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Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas

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ClinicalTrials.gov Identifier: NCT01514201
Recruitment Status : Completed
First Posted : January 23, 2012
Results First Posted : August 13, 2019
Last Update Posted : August 13, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Anaplastic Astrocytoma
Brain Stem Glioma
Childhood Mixed Glioma
Fibrillary Astrocytoma
Giant Cell Glioblastoma
Glioblastoma
Gliosarcoma
Untreated Childhood Anaplastic Astrocytoma
Untreated Childhood Brain Stem Glioma
Untreated Childhood Fibrillary Astrocytoma
Untreated Childhood Giant Cell Glioblastoma
Untreated Childhood Glioblastoma
Untreated Childhood Gliosarcoma
Interventions Radiation: 3-Dimensional Conformal Radiation Therapy
Radiation: Intensity-Modulated Radiation Therapy
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Temozolomide
Drug: Veliparib
Enrollment 66
Recruitment Details Patients up to 21 years of age with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs) were enrolled at Pediatric Brain Tumor Consortium (PBTC) member institutions. The first patient was enrolled on 2/1/2012 and the last patient was enrolled on 01/20/2016.
Pre-assignment Details Of the 66 patients enrolled, 1 phase II patient was deemed ineligible due to an elevated alanine aminotransferase (ALT). Of note, the 6 phase I patients who were treated at the established maximum tolerated dose (MTD) during the phase I portion of the trial were also counted as phase II patients in analyses of phase II objectives.
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD)
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Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Period Title: PHASE I: Veliparib + Radiation Therapy
Started 6 6 6 0
Completed 5 6 6 0
Not Completed 1 0 0 0
Reason Not Completed
Lack of Efficacy             1             0             0             0
Period Title: PHASE I: Maintenance With Veliparib/TMZ
Started 5 6 6 0
Completed 0 0 0 0
Not Completed 5 6 6 0
Reason Not Completed
Adverse Event             0             1             1             0
Lack of Efficacy             4             4             5             0
Withdrawal by Subject             1             1             0             0
Period Title: PHASE II: Veliparib + Radiation Therapy
Started 0 0 0 47
Completed 0 0 0 35
Not Completed 0 0 0 12
Reason Not Completed
Ineligible             0             0             0             1
Adverse Event             0             0             0             2
Death             0             0             0             1
Lack of Efficacy             0             0             0             2
Withdrawal by Subject             0             0             0             6
Period Title: PHASE II: Maintenance With Veliparib/TMZ
Started 0 0 0 35
Completed 0 0 0 2
Not Completed 0 0 0 33
Reason Not Completed
Adverse Event             0             0             0             4
Withdrawal by Subject             0             0             0             7
Lack of Efficacy             0             0             0             22
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD) Total
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Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Total of all reporting groups
Overall Number of Baseline Participants 6 6 6 47 65
Hide Baseline Analysis Population Description
The one ineligible patient enrolled on the protocol was excluded. Summary statistics for baseline characteristics are shown for eligible patients only (n=65).
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 47 participants 65 participants
<=18 years
6
 100.0%
6
 100.0%
6
 100.0%
47
 100.0%
65
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 6 participants 47 participants 65 participants
6.3
(5.3 to 10.4)
10.2
(5.4 to 12.9)
9.2
(2.2 to 15.8)
6.5
(2.5 to 11.6)
6.6
(2.2 to 15.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 47 participants 65 participants
Female
2
  33.3%
3
  50.0%
2
  33.3%
30
  63.8%
37
  56.9%
Male
4
  66.7%
3
  50.0%
4
  66.7%
17
  36.2%
28
  43.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 47 participants 65 participants
Hispanic or Latino
3
  50.0%
0
   0.0%
0
   0.0%
7
  14.9%
10
  15.4%
Not Hispanic or Latino
3
  50.0%
5
  83.3%
5
  83.3%
34
  72.3%
47
  72.3%
Unknown or Not Reported
0
   0.0%
1
  16.7%
1
  16.7%
6
  12.8%
8
  12.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 47 participants 65 participants
American Indian or Alaska Native
1
  16.7%
0
   0.0%
0
   0.0%
1
   2.1%
2
   3.1%
Asian
1
  16.7%
0
   0.0%
0
   0.0%
1
   2.1%
2
   3.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.1%
1
   1.5%
Black or African American
0
   0.0%
2
  33.3%
1
  16.7%
9
  19.1%
12
  18.5%
White
3
  50.0%
3
  50.0%
5
  83.3%
29
  61.7%
40
  61.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
  16.7%
1
  16.7%
0
   0.0%
6
  12.8%
8
  12.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 6 participants 6 participants 6 participants 47 participants 65 participants
6
 100.0%
6
 100.0%
6
 100.0%
47
 100.0%
65
 100.0%
1.Primary Outcome
Title Maximum-tolerated Dose of Veliparib Defined as Highest Dose Level With Fewer Than 2 Dose Limiting Toxicities in 6 Patients as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)
Hide Description The traditional 3+3 dose finding algorithm was used to estimate the maximum-tolerated dose of veliparib given concurrently with radiation therapy. The dose-limiting toxicity observation period was the first 10 weeks of therapy. Dose-limiting toxicities included any grade 4 non-hematologic toxicity, any grade 3 non-hematologic toxicity with a few exceptions (see section 5.2.1.2 of the protocol document), any grade 2 non-hematologic toxicity that persisted for >7 days and considered medically significant that required treatment interruption; grade 3 or higher thrombocytopenia or grade 4 neutropenia; and any Veliparib related adverse event that led to a dose reduction or the permanent cessation of therapy.
Time Frame 10 weeks
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Hide Analysis Population Description
The first 18 patients enrolled on the study were phase I patients used to determine the maximum tolerated dose or the recommended phase II dose and to address other objectives of the phase I component of this trial.
Arm/Group Title Phase I Patients
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The first 18 patients enrolled on the study were phase I patients used to determine the maximum tolerated dose or the recommended phase II dose and to address other objectives of the phase I component of this trial. The starting dose level was 50 mg/m2/dose twice a day (BID) and other dose levels to be studied were 65 and 85 mg/m2/dose BID. If the 85 mg/m2 dose level was tolerated, there was a plan to study a higher dose level (110 mg/m2/dose BID) but only if supported by clinical data.
Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: mg/m2/dose BID
65
2.Primary Outcome
Title Percentage of Participants Observed to Have Unacceptable Toxicity During the Intra-patient Dose Escalation of Temozolomide During Maintenance Therapy (Feasibility Analysis Population)
Hide Description Unacceptable toxicities during maintenance included events at least possibly attributable to Veliparib and temozolomide (TMZ) such as any grade 4 non-hematologic toxicity, any grade 3 non-hematologic toxicity with some exceptions (e.g., grade 3 nausea/vomiting <5 days, grade 3 fever or infection <5 days), grade 3+ thrombocytopenia, grade 4 neutropenia, delay >14 days in starting subsequent cycle due to neutrophil <1,000/mm3 or platelet <100,000/mm3. Maintenance therapy was initiated with 25 mg/m2 Veliparib and 135 mg/m2 of TMZ, with the possibility to escalate TMZ to 175 mg/m2 and 200 mg/m2 in courses 2 and 3, respectively, if no unacceptable toxicities occurred following one course of treatment at each of the dose levels to be tested. Intra-patient dose escalation to a given dose (135, 175, or 200 mg/m2) was halted based on rules employed in 3+3 designs. This dose escalation was intended for all patients but was halted early, during the phase I portion, as it was not well tolerated.
Time Frame 28 days per treatment cycle
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Hide Analysis Population Description
Patients were combined across dose levels since they received the same maintenance therapy. Though this objective was intended for all patients, only the first 12 enrolled were included as the dose-escalation stopped early. 1 of the first 12 patients did not start maintenance due to early progression, so 11 patients started dose level 1.
Arm/Group Title Dose Level 1 (135 mg/m2) Dose Level 2 (175 mg/m2) Dose Level 3 (200 mg/m2)
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Participants in the feasibility analysis population that started dose level 1 of the intra-patient dose escalation during maintenance (Veliparib 25 mg/m2 twice a day (BID) + temozolomide 135 mg/m2/day)
Participants in the feasibility analysis population that started dose level 2 of the intra-patient dose escalation during maintenance (Veliparib 25 mg/m2 twice a day (BID) + temozolomide 175 mg/m2/day)
Participants in the feasibility analysis population that started dose level 1 of the intra-patient dose escalation during maintenance (Veliparib 25 mg/m2 twice a day (BID) + temozolomide 200 mg/m2/day)
Overall Number of Participants Analyzed 11 5 3
Measure Type: Number
Unit of Measure: % of participants
9 40 67
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dose Level 1 (135 mg/m2), Dose Level 2 (175 mg/m2), Dose Level 3 (200 mg/m2)
Comments Intra-patient dose escalation of temozolomide during maintenance was assessed based on similar rules employed in traditional 3+3 designs. For example intra-patient dose escalation would be halted if at any time 2 out of first 2-6 patients experienced dose-modifying toxicities at a given dose level or if 4 out of first 12 patients experienced dose-modifying toxicities at a given dose level.
Type of Statistical Test Other
Comments This was descriptive in nature. Two of the first 5 patients who were escalated to 175 mg/m2 of temozolomide during the maintenance intra-patient dose escalation had dose-modifying toxicities (DMTs). Since the ad hoc stopping rule was met, intra-patient dose escalation was halted and all subsequent patients were to receive 135 mg/m2 of temozolomide during maintenance.
Method of Estimation Estimation Parameter Percentage of patients with DMTs
Estimated Value 40
Estimation Comments [Not Specified]
3.Primary Outcome
Title Overall Survival
Hide Description Overall survival was defined as the interval from date on treatment to date of death from any cause or to date of last follow-up. Patients who had not failed (died) at the time of analyses were censored at their last date of contact. The method of Kaplan and Meier was used to estimate overall survival. The 3-year estimate with a 95% confidence interval is reported.
Time Frame Time from initiation of therapy to the date of death from any cause or to the date patient was known to be alive for surviving patients, assessed to up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
53 patients were evaluable for outcome analyses (47 phase II patients + 6 phase I patients treated at the MTD). 50 patients were evaluable; 1 patient withdrew prior to beginning protocol therapy and 2 patients did not receive adequate study drug to be evaluable for efficacy. To be evaluable patients had to receive at least one dose of Veliparib.
Arm/Group Title Phase II Patients + Phase I MTD Patients
Hide Arm/Group Description:
Phase II patients were those enrolled after the maximum tolerated dose was established in the phase I portion of this trial. Six patients enrolled as phase I patients but who were treated with the established maximum tolerated dose of 65 mg/m2/day twice a day (BID) were also considered phase II patients. There were 53 eligible phase II patients (including the latter six patients). Fifty (50) of these patients were evaluable for outcome analyses as 1 patient withdrew prior to beginning protocol therapy and 2 other patients did not receive adequate study drug to be evaluable for efficacy. To be evaluable for assessing overall survival, patients had to receive at least one dose of Veliparib.
Overall Number of Participants Analyzed 50
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent probability
5.3
(0.0 to 12.4)
4.Primary Outcome
Title Number of Phase I Patients Who Experienced Dose Limiting Toxicities (DLTs)
Hide Description DLTs were defined as any of the following adverse events that were at least possibly attributable to Veliparib observed during the dose finding phase (the first 10 weeks of therapy). Hematologic dose limiting toxicities included grade 3 and higher thrombocytopenia or grade 4 neutropenia. Non-hematologic dose limiting toxicities included any grade 4 non-hematologic toxicity, any grade 3 non-hematologic toxicity with some exceptions (e.g., nausea and vomiting of <5 days; fever or infection of <5 days; hypophosphatemia, hypokalemia, hypocalcemia or hypomagnesemia responsive to oral supplementation; elevation of transaminases that return to levels meeting eligibility criteria within 7 days), or any grade non-hematologic toxicity that persisted for >7 days and considered medically significant or sufficiently intolerable by patients that required treatment interruption.
Time Frame 10 weeks
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg)
Hide Arm/Group Description:

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Overall Number of Participants Analyzed 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
1
  16.7%
0
   0.0%
3
  50.0%
5.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS was defined as the interval from date of treatment initiation to date of first event (disease progression or relapse, second malignancy or death from any cause). Patients who had not failed at the time of analyses were censored at their last date of contact. The method of Kaplan and Meier was used to estimate PFS. A 3-year estimate with a 95% confidence interval is reported.
Time Frame Time from initiation of treatment to the earliest date of failure (disease progression, death from any cause, or second malignancy), assessed up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
53 patients were evaluable for outcome analyses (47 phase II patients + 6 phase I patients treated at the MTD). 50 patients were evaluable; 1 patient withdrew prior to beginning protocol therapy and 2 patients did not receive adequate study drug to be evaluable for efficacy. To be evaluable patients had to receive at least one dose of Veliparib.
Arm/Group Title Phase II Patients + Phase I MTD Patients
Hide Arm/Group Description:
Phase II patients were those enrolled after the maximum tolerated dose was established in the phase I portion of this trial. Six patients enrolled as phase I patients but who were treated with the established maximum tolerated dose of 65 mg/m2/day twice a day (BID) were also considered phase II patients. There were 53 eligible phase II patients (including the latter six patients). Fifty (50) of these patients were evaluable for outcome analyses as 1 patient withdrew prior to beginning protocol therapy and 2 other patients did not receive adequate study drug to be evaluable for efficacy. To be evaluable for assessing PFS, patients had to receive at least one dose of Veliparib.
Overall Number of Participants Analyzed 50
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent probability
2.9
(0.0 to 6.8)
6.Secondary Outcome
Title Percentage of Patients With Pseudo Progression
Hide Description For participants that showed possible tumor progression (pseudo progression) on magnetic resonance imaging (MRI) during the first 6 months of therapy, treating physicians had the option of allowing patients to remain on therapy and repeating the disease assessment in 4-6 weeks. If the repeat MRI at 4-6 weeks showed disease progression, the patient was noted to have true disease progression (and the progression date corresponded to that of the first MRI). If the repeat MRI at 4-6 weeks did not show disease progression, then the patient was noted to have pseudo progression. The percentage of patients observed to have experienced pseudo progression was provided with a 95% confidence interval.
Time Frame Up to 6 months
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD)
Hide Arm/Group Description:

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Overall Number of Participants Analyzed 6 6 6 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
33.3
(6.3 to 72.9)
16.7
(0.9 to 59.8)
0
(0.0 to 40.2)
12.8
(5.7 to 24.5)
7.Secondary Outcome
Title Maximum Concentration of Veliparib (Cmax) on Days 1 and 4 (Measured in ng/mL) [Pharmacokinetic Parameter]
Hide Description During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. Cmax measures the highest concentration of drug.
Time Frame Up to day 4
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic studies were optional for the phase II portion of the study. Pharmacokinetic data were not available for all patients as indicated in the outcome measure data table below.
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD)
Hide Arm/Group Description:

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Overall Number of Participants Analyzed 6 6 6 47
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1, Cmax (ng/mL) Number Analyzed 6 participants 6 participants 4 participants 25 participants
519  (241) 843  (364) 1074  (372) 844  (279)
Day 4, Cmax (ng/mL) Number Analyzed 6 participants 6 participants 4 participants 19 participants
409  (84) 788  (435) 954  (348) 717  (232)
8.Secondary Outcome
Title Mean Apparent Clearance (CL/F) for Veliparib [Pharmacokinetic Parameter]
Hide Description During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis.
Time Frame Up to day 4
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic studies were optional for the phase II portion of the study. 6/6 phase I dose level 1 patients, 6/6 phase I dose level 2 patients, 4/6 phase I dose level 3 patients, and 25/47 phase II patients had this data available.
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD)
Hide Arm/Group Description:

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Overall Number of Participants Analyzed 6 6 4 25
Mean (Standard Deviation)
Unit of Measure: L/m^2/h
16.1  (8.1) 13.2  (4.3) 15.8  (8.3) 11.7  (8.8)
9.Secondary Outcome
Title Maximum Concentration of Veliparib (Cmax) on Day 1 (Measured in μM) [Pharmacokinetic Parameter]
Hide Description During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. Cmax measures the highest concentration of drug.
Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic studies were optional for the phase II portion of the study. Pharmacokinetic data were not available for all patients. 6/6 phase I dose level 1, 6/6 phase I dose level 2, 4/6 phase I dose level 3, and 25/47 phase II patients had day 4 Cmax data available.
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD)
Hide Arm/Group Description:

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Overall Number of Participants Analyzed 6 6 4 25
Mean (Standard Deviation)
Unit of Measure: μM
2.12  (0.98) 3.45  (1.49) 4.40  (1.52) 3.45  (1.14)
10.Secondary Outcome
Title Apparent Volume of Distribution (Vd/F) for Veliparib [Pharmacokinetic Parameter]
Hide Description During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis.
Time Frame Up to day 4
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic studies were optional for the phase II portion of the study. 6/6 phase I dose level 1 patients, 6/6 phase I dose level 2 patients, 4/6 phase I dose level 3 patients, and 25/47 phase II patients had this data available.
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD)
Hide Arm/Group Description:

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Overall Number of Participants Analyzed 6 6 4 25
Mean (Standard Deviation)
Unit of Measure: L/m^2
75.4  (29.2) 56.1  (25.4) 63.9  (10.6) 73.1  (109.7)
11.Secondary Outcome
Title Terminal Half-life (t1/2) for Veliparib [Pharmacokinetic Parameter]
Hide Description During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis.
Time Frame Up to day 4
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic studies were optional for the phase II portion of the study. 6/6 phase I dose level 1 patients, 6/6 phase I dose level 2 patients, 4/6 phase I dose level 3 patients, and 25/47 phase II patients had this data available.
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD)
Hide Arm/Group Description:

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Overall Number of Participants Analyzed 6 6 4 25
Mean (Standard Deviation)
Unit of Measure: Hour
5.18  (6.34) 2.62  (0.76) 4.45  (4.80) 2.18  (2.71)
12.Secondary Outcome
Title Trough for Veliparib [Pharmacokinetic Parameter]
Hide Description During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis.
Time Frame Up to day 4
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic studies were optional for the phase II portion of the study. 6/6 phase I dose level 1 patients, 5/6 phase I dose level 2 patients, 4/6 phase I dose level 3 patients, and 20/47 phase II patients had this data available.
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD)
Hide Arm/Group Description:

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Overall Number of Participants Analyzed 6 5 4 20
Mean (Standard Deviation)
Unit of Measure: ng/mL
58  (19) 140  (173) 163  (97) 84  (42)
13.Other Pre-specified Outcome
Title Percentage of Participants With Significant Changes in Poly(ADP-ribose) Polymerase (PARP) Levels Post-Veliparib, as Measured in Peripheral Blood Monocytes (PBMCs)
Hide Description Blood samples were collected from patients and assessed pre- and post-Veliparib to assess treatment-induced changes. A significant change in PBMC PARP level was arbitrarily defined as a >50% increase or decrease from the pre-treatment level, documented at week 6 and/or week 11 after starting protocol therapy.
Time Frame Baseline and up to 11 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Only 27 patients had pre- and post-Veliparib samples available in order to assess treatment-related changes. Two of the patients had inconsistent changes in post-Veliparib PARP levels and therefore were excluded from the analysis, leaving 25 patients for this objective.
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD)
Hide Arm/Group Description:

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Overall Number of Participants Analyzed 3 4 4 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
100
(37 to 100)
100
(47 to 100)
75
(25 to 99)
36
(15 to 63)
14.Other Pre-specified Outcome
Title Change in Non-homologous End-joining (NHEJ) Activity as Measured in Peripheral Blood Monocytes (PBMCs)
Hide Description Levels of non-homologous end-joining (NHEJ) activity were to be calculated. Cox models to explore associations between the levels of NHEJ and outcome (progression-free survival and overall survival) were planned, in addition to looking at associations between Poly(ADP-ribose) polymerase (PARP) activity and NHEJ levels.
Time Frame Baseline to up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
These data were not available as the lab did not perform these analyses. There are no plans to perform these analyses.
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD)
Hide Arm/Group Description:

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
15.Other Pre-specified Outcome
Title Change in Level of Gamma-H2A Histone Family, Member X (H2AX) Measured in PBMCs
Hide Description Levels of gamma-H2A histone family, member X (H2AX) were to be calculated. Cox models to explore associations between the levels of gamma-H2AX and outcome (progression-free survival and overall survival) were planned, in addition to looking at associations between Poly(ADP-ribose) polymerase (PARP) activity and gamma-H2AX levels.
Time Frame Baseline to up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
These data were not available as the lab did not perform these analyses. There are no plans to perform these analyses.
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD)
Hide Arm/Group Description:

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
16.Other Pre-specified Outcome
Title Levels of Urinary Biomarkers
Hide Description Urine samples were analyzed for a panel of biomarkers. Netrin-1 levels were determined by ELISA. Levels of matrix metalloproteinase 3 (MMP3) and basic fibroblast growth factor (bFGF) were analyzed using custom Luminex® screening assays. Tissue inhibitor of metalloproteinase 1 (TIMP1) levels were analyzed using a Luminex® performance assay. Protein concentrations are given in picograms per microgram (pg/μg), and were determined by dividing the concentration of the target protein in the sample (pg/mL) by the concentration of total protein in the sample (μg/mL) as a normalization measure.
Time Frame Baseline to up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Not all patients had urine samples at each time point.
Arm/Group Title Phase I, Dose Level 1 (50 mg) Phase I, Dose Level 2 (65 mg) Phase I, Dose Level 3 (85 mg) Phase II (MTD)
Hide Arm/Group Description:

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

Overall Number of Participants Analyzed 6 6 6 47
Median (Full Range)
Unit of Measure: pg/μg
MMP3 at pre-study Number Analyzed 5 participants 6 participants 3 participants 35 participants
2.0
(0.9 to 3.2)
1.0
(0.4 to 2.1)
0.0
(0.0 to 2.6)
1.1
(0.0 to 7.6)
MMP3 at week 10-11 Number Analyzed 5 participants 5 participants 5 participants 24 participants
1.4
(0.7 to 4.0)
1.0
(0.0 to 2.9)
0.8
(0.4 to 3.5)
2.6
(0.0 to 9.8)
MMP3 at week 18 Number Analyzed 3 participants 3 participants 3 participants 18 participants
4.3
(4.2 to 4.6)
1.7
(1.3 to 2.4)
0.7
(0.5 to 1.0)
2.3
(0.0 to 15.8)
MMP3 at week 26 Number Analyzed 2 participants 2 participants 2 participants 11 participants
2.9
(2.8 to 3.0)
0.4
(0.3 to 0.5)
1.0
(1.0 to 1.1)
3.0
(0.2 to 6.4)
Netrin-1 at pre-study Number Analyzed 5 participants 6 participants 3 participants 35 participants
0.1
(0.0 to 0.3)
0.1
(0.1 to 0.2)
0.1
(0.0 to 0.3)
0.1
(0.0 to 0.9)
Netrin-1 at week 10-11 Number Analyzed 5 participants 4 participants 4 participants 24 participants
0.1
(0.1 to 0.3)
0.1
(0.0 to 0.3)
0.1
(0.0 to 0.5)
0.0
(0.0 to 0.3)
Netrin-1 at week 18 Number Analyzed 3 participants 2 participants 3 participants 18 participants
0.3
(0.2 to 0.3)
0.1
(0.1 to 0.1)
0.0
(0.0 to 0.0)
0.1
(0.0 to 0.6)
Netrin-1 at week 26 Number Analyzed 2 participants 2 participants 1 participants 11 participants
0.4
(0.4 to 0.4)
0.2
(0.2 to 0.3)
0.0
(0.0 to 0.0)
0.0
(0.0 to 1.0)
TIMP1 at pre-study Number Analyzed 5 participants 6 participants 3 participants 35 participants
3.4
(3.1 to 9.0)
9.9
(1.4 to 18.7)
10.8
(1.5 to 39.7)
7.3
(1.9 to 16.8)
TIMP1 at week 10-11 Number Analyzed 5 participants 6 participants 5 participants 24 participants
6.2
(4.0 to 22.4)
11.9
(0.0 to 40.5)
12.3
(7.8 to 143.7)
7.5
(3.5 to 20.3)
TIMP1 at week 18 Number Analyzed 3 participants 3 participants 3 participants 18 participants
10.7
(2.9 to 18.1)
7.7
(5.8 to 9.6)
14.8
(12.0 to 61.9)
7.1
(2.4 to 44.7)
TIMP1 at week 26 Number Analyzed 2 participants 2 participants 2 participants 11 participants
7.3
(7.2 to 7.4)
5.2
(2.6 to 7.8)
32.8
(4.9 to 60.7)
10.7
(2.4 to 30.8)
bFGF at pre-study Number Analyzed 5 participants 6 participants 3 participants 35 participants
3.1
(1.3 to 7.8)
1.9
(1.0 to 3.7)
1.2
(0.0 to 3.0)
4.5
(0.0 to 18.5)
bFGF at week 10-11 Number Analyzed 5 participants 5 participants 5 participants 24 participants
3.6
(3.3 to 9.3)
2.1
(0.8 to 6.4)
1.8
(0.8 to 2.7)
3.5
(0.0 to 9.4)
bFGF at week 18 Number Analyzed 3 participants 3 participants 3 participants 18 participants
10.3
(7.1 to 10.9)
3.5
(1.5 to 5.2)
1.3
(0.6 to 1.4)
4.4
(0.0 to 40.8)
bFGF at week 26 Number Analyzed 2 participants 2 participants 2 participants 11 participants
7.7
(7.0 to 8.4)
0.9
(0.6 to 1.2)
1.1
(1.1 to 1.1)
4.5
(0.3 to 66.0)
Time Frame Approximately 1 year after starting treatment
Adverse Event Reporting Description Adverse events (AEs) were graded according to CTCAE v4.0. AEs collected per protocol included: a) grade 1 and 2 AEs if attribution was at least possibly related to veliparib and b) all grade 3+ AEs on treatment and within 30 days off treatment. All AEs collected are reported. As the intra-patient escalation of TMZ during maintenance was by course (rather than patient) and was halted early (only 5(3) patients escalated to 175(200) mg/m2), AEs were not reported separately by course-specific doses.
 
Arm/Group Title Phase I, Dose Level 1 (50 mg/m2) Phase I, Dose Level 2 (65 mg/m2) Phase I, Dose Level 3 (85 mg/m2) Phase II (MTD)
Hide Arm/Group Description

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent radiation (3D-CRT or IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent radiation (3D-CRT or IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Dose Escalation: Patients receive veliparib orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent radiation (3D-CRT or IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide (TMZ) PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early as it was not well tolerated.

Patients receive veliparib at the maximum tolerated dose (MTD) orally (PO) twice a day (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent radiation (3D-CRT or IMRT) once a day (QD) 5 days a week for 6-7 weeks.

Maintenance Therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. All patients start maintenance with 25 mg/m2 BID of veliparib and 135 mg/m2/day of TMZ. Intra-patient escalation of TMZ to 175 mg/m2/day and 200 mg/m2/day in subsequent courses was allowed for patients with minimal toxicities. However this intra-patient dose escalation was halted early (before the phase II study was initiated) as it was not well tolerated.

All-Cause Mortality
Phase I, Dose Level 1 (50 mg/m2) Phase I, Dose Level 2 (65 mg/m2) Phase I, Dose Level 3 (85 mg/m2) Phase II (MTD)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)      5/6 (83.33%)      6/6 (100.00%)      40/47 (85.11%)    
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Phase I, Dose Level 1 (50 mg/m2) Phase I, Dose Level 2 (65 mg/m2) Phase I, Dose Level 3 (85 mg/m2) Phase II (MTD)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/6 (83.33%)      2/6 (33.33%)      2/6 (33.33%)      19/47 (40.43%)    
Ear and labyrinth disorders         
Hearing impaired   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Endocrine disorders         
Cushingoid   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Eye disorders         
Papilledema   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Gastrointestinal disorders         
Abdominal pain   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/47 (0.00%)  0
Constipation   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 2/47 (4.26%)  2
Abdominal distension   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Dysphagia   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/47 (6.38%)  3
Pancreatitis   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Vomiting   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 4/47 (8.51%)  4
General disorders         
Fever   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 1/47 (2.13%)  1
Death NOS   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Fatigue   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 5/47 (10.64%)  5
Gait disturbance   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Pain   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Infections and infestations         
Catheter related infection   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Infections and infestations - Other, specify   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Lung infection   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/47 (4.26%)  2
Urinary tract infection   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/47 (4.26%)  2
Injury, poisoning and procedural complications         
Postoperative hemorrhage   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Investigations         
Neutrophil count decreased   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Platelet count decreased   2/6 (33.33%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Weight loss   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/47 (0.00%)  0
Lipase increased   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Lymphocyte count decreased   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/47 (4.26%)  2
Serum amylase increased   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Metabolism and nutrition disorders         
Anorexia   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/47 (0.00%)  0
Hyponatremia   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/47 (2.13%)  1
Acidosis   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 4/47 (8.51%)  4
Nervous system disorders         
Headache   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 3/47 (6.38%)  3
Hydrocephalus   3/6 (50.00%)  3 1/6 (16.67%)  1 1/6 (16.67%)  1 8/47 (17.02%)  9
Intracranial hemorrhage   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Nervous system disorders - Other, specify   1/6 (16.67%)  3 0/6 (0.00%)  0 1/6 (16.67%)  1 1/47 (2.13%)  1
Depressed level of consciousness   0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2 2/47 (4.26%)  2
Encephalopathy   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Lethargy   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Seizure   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 2/47 (4.26%)  2
Ataxia   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/47 (4.26%)  2
Cerebrospinal fluid leakage   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Cognitive disturbance   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Dizziness   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Dysarthria   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 4/47 (8.51%)  4
Hypoglossal nerve disorder   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Reversible posterior leukoencephalopathy syndrome   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Somnolence   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/47 (6.38%)  3
Renal and urinary disorders         
Hematuria   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Renal calculi   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Urinary incontinence   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Respiratory, thoracic and mediastinal disorders         
Atelectasis   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Respiratory failure   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 4/47 (8.51%)  4
Hypoxia   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/47 (4.26%)  2
Respiratory, thoracic and mediastinal disorders - Other, specify   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Vascular disorders         
Hypertension   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/47 (6.38%)  3
Thromboembolic event   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase I, Dose Level 1 (50 mg/m2) Phase I, Dose Level 2 (65 mg/m2) Phase I, Dose Level 3 (85 mg/m2) Phase II (MTD)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      6/6 (100.00%)      6/6 (100.00%)      46/47 (97.87%)    
Blood and lymphatic system disorders         
Anemia   4/6 (66.67%)  11 4/6 (66.67%)  20 6/6 (100.00%)  13 27/47 (57.45%)  59
Febrile neutropenia   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Cardiac disorders         
Palpitations   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Sinus bradycardia   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/47 (0.00%)  0
Sinus tachycardia   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Ear and labyrinth disorders         
Ear pain   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
External ear inflammation   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Endocrine disorders         
Cushingoid   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/47 (2.13%)  1
Eye disorders         
Blurred vision   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/47 (2.13%)  1
Eye disorders - Other, specify   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/47 (2.13%)  1
Eye pain   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/47 (2.13%)  1
Gastrointestinal disorders         
Abdominal pain   0/6 (0.00%)  0 2/6 (33.33%)  3 1/6 (16.67%)  1 4/47 (8.51%)  4
Constipation   3/6 (50.00%)  4 5/6 (83.33%)  6 1/6 (16.67%)  1 14/47 (29.79%)  19
Diarrhea   2/6 (33.33%)  3 0/6 (0.00%)  0 1/6 (16.67%)  1 1/47 (2.13%)  1
Dry mouth   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Dysphagia   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 5/47 (10.64%)  5
Mucositis oral   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Nausea   5/6 (83.33%)  7 5/6 (83.33%)  7 4/6 (66.67%)  7 14/47 (29.79%)  23
Rectal pain   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Stomach pain   1/6 (16.67%)  4 0/6 (0.00%)  0 0/6 (0.00%)  0 2/47 (4.26%)  3
Vomiting   2/6 (33.33%)  3 4/6 (66.67%)  11 4/6 (66.67%)  12 21/47 (44.68%)  35
General disorders         
Fatigue   4/6 (66.67%)  4 4/6 (66.67%)  5 3/6 (50.00%)  7 15/47 (31.91%)  26
Fever   0/6 (0.00%)  0 1/6 (16.67%)  1 2/6 (33.33%)  2 0/47 (0.00%)  0
Gait disturbance   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Hypothermia   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/47 (0.00%)  0
Infusion related reaction   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Non-cardiac chest pain   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Infections and infestations         
Infections and infestations - Other, specify   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/47 (0.00%)  0
Urinary tract infection   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 2/47 (4.26%)  3
Injury, poisoning and procedural complications         
Dermatitis radiation   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/47 (0.00%)  0
Fall   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Investigations         
Alanine aminotransferase increased   3/6 (50.00%)  3 2/6 (33.33%)  2 0/6 (0.00%)  0 23/47 (48.94%)  33
Alkaline phosphatase increased   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/47 (4.26%)  2
Aspartate aminotransferase increased   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 12/47 (25.53%)  22
Blood bilirubin increased   1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 3/47 (6.38%)  3
Creatinine increased   0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 2/47 (4.26%)  3
GGT increased   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Hemoglobin increased   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 5/47 (10.64%)  11
Lymphocyte count decreased   5/6 (83.33%)  15 6/6 (100.00%)  34 6/6 (100.00%)  27 44/47 (93.62%)  260
Neutrophil count decreased   3/6 (50.00%)  8 4/6 (66.67%)  17 5/6 (83.33%)  24 19/47 (40.43%)  66
Platelet count decreased   5/6 (83.33%)  14 5/6 (83.33%)  30 4/6 (66.67%)  18 23/47 (48.94%)  72
Weight gain   2/6 (33.33%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 3/47 (6.38%)  4
Weight loss   0/6 (0.00%)  0 1/6 (16.67%)  1 2/6 (33.33%)  3 4/47 (8.51%)  4
White blood cell decreased   5/6 (83.33%)  17 5/6 (83.33%)  36 5/6 (83.33%)  22 36/47 (76.60%)  131
Metabolism and nutrition disorders         
Anorexia   1/6 (16.67%)  1 2/6 (33.33%)  3 4/6 (66.67%)  4 10/47 (21.28%)  14
Dehydration   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Hypercalcemia   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Hyperglycemia   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 3/47 (6.38%)  4
Hyperkalemia   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 5/47 (10.64%)  7
Hypermagnesemia   3/6 (50.00%)  3 2/6 (33.33%)  2 1/6 (16.67%)  2 8/47 (17.02%)  11
Hypernatremia   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 2/47 (4.26%)  4
Hypoalbuminemia   1/6 (16.67%)  1 2/6 (33.33%)  3 0/6 (0.00%)  0 18/47 (38.30%)  33
Hypocalcemia   2/6 (33.33%)  2 2/6 (33.33%)  6 2/6 (33.33%)  2 9/47 (19.15%)  21
Hypokalemia   4/6 (66.67%)  8 0/6 (0.00%)  0 3/6 (50.00%)  4 14/47 (29.79%)  22
Hyponatremia   1/6 (16.67%)  1 1/6 (16.67%)  1 2/6 (33.33%)  3 6/47 (12.77%)  6
Hypophosphatemia   2/6 (33.33%)  2 1/6 (16.67%)  1 4/6 (66.67%)  5 14/47 (29.79%)  20
Metabolism and nutrition disorders - Other, specify   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/47 (4.26%)  2
Musculoskeletal and connective tissue disorders         
Arthralgia   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Flank pain   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Muscle weakness left-sided   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 3/47 (6.38%)  6
Muscle weakness lower limb   1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Muscle weakness right-sided   0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 1/47 (2.13%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify   1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 2/47 (4.26%)  2
Nervous system disorders         
Abducens nerve disorder   1/6 (16.67%)  1 1/6 (16.67%)  1 1/6 (16.67%)  1 5/47 (10.64%)  5
Ataxia   4/6 (66.67%)  4 3/6 (50.00%)  4 1/6 (16.67%)  1 5/47 (10.64%)  9
Dizziness   1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 1/47 (2.13%)  1
Dysarthria   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 4/47 (8.51%)  5
Dysgeusia   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Facial nerve disorder   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 2/47 (4.26%)  2
Glossopharyngeal nerve disorder   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/47 (0.00%)  0
Headache   2/6 (33.33%)  3 3/6 (50.00%)  4 4/6 (66.67%)  5 7/47 (14.89%)  12
IVth nerve disorder   0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 1/47 (2.13%)  1
Oculomotor nerve disorder   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/47 (2.13%)  1
Paresthesia   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/47 (2.13%)  1
Somnolence   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/47 (0.00%)  0
Spasticity   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/47 (2.13%)  1
Tremor   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/47 (2.13%)  1
Psychiatric disorders         
Anxiety   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/47 (0.00%)  0
Depression   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Insomnia   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 4/47 (8.51%)  5
Personality change   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Renal and urinary disorders         
Hematuria   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/47 (2.13%)  1
Urinary frequency   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Urinary retention   1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Urinary tract pain   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/47 (2.13%)  1
Respiratory, thoracic and mediastinal disorders         
Cough   3/6 (50.00%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0 4/47 (8.51%)  5
Dyspnea   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/47 (0.00%)  0
Epistaxis   1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 1/47 (2.13%)  1
Skin and subcutaneous tissue disorders         
Alopecia   0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 5/47 (10.64%)  5
Dry skin   2/6 (33.33%)  2 1/6 (16.67%)  1 0/6 (0.00%)  0 1/47 (2.13%)  1
Pruritus   1/6 (16.67%)  1 1/6 (16.67%)  1 1/6 (16.67%)  1 2/47 (4.26%)  2
Rash maculo-papular   1/6 (16.67%)  1 2/6 (33.33%)  2 2/6 (33.33%)  2 5/47 (10.64%)  6
Skin hyperpigmentation   0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/47 (2.13%)  2
Vascular disorders         
Hypertension   1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/47 (4.26%)  5
Hypotension   0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/47 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Catherine Billups
Organization: St. Jude Children's Research Hospital
Phone: 901-595-3709
EMail: catherine.billups@stjude.org
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01514201     History of Changes
Obsolete Identifiers: NCT01507324
Other Study ID Numbers: NCI-2012-00082
NCI-2012-00082 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PBTC-033
12-C-0213
CDR0000717423
P12978
PBTC-033 ( Other Identifier: Pediatric Brain Tumor Consortium )
PBTC-033 ( Other Identifier: CTEP )
U01CA081457 ( U.S. NIH Grant/Contract )
UM1CA081457 ( U.S. NIH Grant/Contract )
First Submitted: January 16, 2012
First Posted: January 23, 2012
Results First Submitted: June 11, 2019
Results First Posted: August 13, 2019
Last Update Posted: August 13, 2019