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Veliparib and Temozolomide in Treating Patients With Recurrent Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01026493
Recruitment Status : Completed
First Posted : December 4, 2009
Results First Posted : July 2, 2017
Last Update Posted : July 2, 2017
Sponsor:
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Brain and Central Nervous System Tumors
Interventions Drug: temozolomide 60 mg x 21 days
Drug: temozolomide 75 mg x 21 days
Drug: ABT-888 20 mg x 21 days
Drug: ABT-888 40 mg x 21 days
Drug: Temozolomide 150 mg x 5 days
Drug: ABT-888 40 mg x 5 days
Enrollment 257
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase I: Dose Level 1 Phase I: Dose Level 2a Phase I: Dose Level 2b Phase I: Dose Level 3 Phase II: Arm 1/BEV-NAIVE Phase II: Arm 2/BEV-NAIVE Phase II: Arm 1/BEV-FAILURE Phase II: Arm 2/BEV-FAILURE
Hide Arm/Group Description ABT-888 20 mg x 21 days plus temozolomide 60 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 60 mg x 21 days ABT-888 20 mg x 21 days plus temozolomide 75 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days ABT-888 40 mg x 5 days plus temozolomide 75 mg x 5 days ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days
Period Title: Overall Study
Started 8 [1] 7 9 8 75 76 36 38
Completed 8 6 9 8 73 73 32 37
Not Completed 0 1 0 0 2 3 4 1
Reason Not Completed
Protocol Violation             0             1             0             0             2             3             4             1
[1]
Subjects with data available for the primary analysis are considered to have completed the study.
Arm/Group Title Phase I: Dose Level 1 Phase I: Dose Level 2a Phase I: Dose Level 2b Phase I: Dose Level 3 Phase II: Arm 1/BEV-NAIVE Phase II: Arm 2/BEV-NAIVE Phase II: Arm 1/BEV-FAILURE Phase II: Arm 2/BEV-FAILURE Total
Hide Arm/Group Description ABT-888 20 mg x 21 days plus temozolomide 60 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 60 mg x 21 days ABT-888 20 mg x 21 days plus temozolomide 75 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days ABT-888 40 mg x 5 days plus temozolomide 75 mg x 5 days ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days Total of all reporting groups
Overall Number of Baseline Participants 8 6 9 8 73 73 32 37 246
Hide Baseline Analysis Population Description
Eligible patients
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 8 participants 6 participants 9 participants 8 participants 73 participants 73 participants 32 participants 37 participants 246 participants
48
(20 to 63)
51
(48 to 63)
53
(18 to 67)
41
(20 to 81)
56
(21 to 77)
56
(20 to 81)
56
(20 to 70)
57
(38 to 77)
56
(18 to 81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 9 participants 8 participants 73 participants 73 participants 32 participants 37 participants 246 participants
Female
2
  25.0%
1
  16.7%
5
  55.6%
4
  50.0%
20
  27.4%
26
  35.6%
12
  37.5%
14
  37.8%
84
  34.1%
Male
6
  75.0%
5
  83.3%
4
  44.4%
4
  50.0%
53
  72.6%
47
  64.4%
20
  62.5%
23
  62.2%
162
  65.9%
1.Primary Outcome
Title Phase 1: Maximum Tolerated Dose (MTD)
Hide Description Dose limiting toxicity (DLT) = any of the following events within 1st 8 weeks of treatment attributable to study drugs: Any grade (gr) 3/4 thrombocytopenia, gr 4 anemia, gr 3 neutropenia with fever (>100.4). gr 4 neutropenia lasting > 7 days; Any non-hematologic (NH) gr 3+ toxicity (TOX), excluding alopecia, despite maximal medical therapy (MLT); NH TOX such as rash, nausea, vomiting, diarrhea, mucositis, hypophosphatemia, and hypertension will only be considered DLTs if they remain gr 3+ despite MLT; 2nd occurrence of thromboembolism; Failure to recover from TOX (<= gr 1) to be eligible for re-treatment with study drugs <= 14 days of last dose of either drug; Any episode of non-infectious radiologically observed pneumonitis gr 2-4 any duration. Dose level will be considered acceptable if <= 1 of the 1st 6 eligible patients experiences a DLT. If current level is considered acceptable, dose escalation occurs. Otherwise preceding acceptable dose level will be declared the MTD.
Time Frame Start of treatment to 8 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients who started study treatment
Arm/Group Title Phase I: Dose Level 1 Phase I: Dose Level 2a Phase I: Dose Level 2b Phase I: Dose Level 3
Hide Arm/Group Description:
ABT-888 20 mg x 21 days plus temozolomide 60 mg x 21 days
ABT-888 40 mg x 21 days plus temozolomide 60 mg x 21 days
ABT-888 20 mg x 21 days plus temozolomide 75 mg x 21 days
ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days
Overall Number of Participants Analyzed 8 6 9 8
Measure Type: Number
Unit of Measure: participants
1 0 1 1
2.Primary Outcome
Title Phase II: 6-month Progression-free Survival (PFS) Rate for Patients With Measurable Disease After Surgery
Hide Description For patients with measureable disease after surgery: Progression defined as ≥ 25% increase in size of enhancing tumor or any new tumor; or neurologically worse, and steroids stable/increased. Bevacizumab (BEV)-naïve group: p0= 15% as estimate of 6-mo. PFS [null hypothesis (NH)], p1= 30%, with a 15% absolute increase [alternative hypothesis (AH)]. Error rates of 10% alpha and 10% beta. If <= 11 patients experience 6-month PFS of the first 53 analyzable patients, then do not reject the null hypothesis that the 6-month PFS rate of experimental arm is less than 15%; BEV-failure group: p0 = 2% as a conservative estimate of 6-month PFS [NH], p1 = 15%, with a 13% absolute increase [AH]. Using first 26 analyzable subjects for each experimental arm, there is >= 90% power to detect >= 15% increase at a significance level of 0.10, using a 1-sided binomial test. If >= 2 patients (8%) are progression free at 6 mo., then claim this regimen to be promising in the patient group.
Time Frame Randomization to 6 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized patients with measurable disease after surgery, at least one cycle of treatment, evaluable for 6 month PFS, and within the required sample size (i.e. the first 53 BEV-naive patients and the first 26 BEV-failure patients- the number of patients will be less than sample size if not enough patients meet the criteria).
Arm/Group Title Phase II: Arm 1/BEV-NAIVE Phase II: Arm 2/BEV-NAIVE Phase II: Arm 1/BEV-FAILURE Phase II: Arm 2/BEV-FAILURE
Hide Arm/Group Description:
ABT-888 40 mg x 5 days plus temozolomide 75 mg x 5 days
ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days
ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days
ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days
Overall Number of Participants Analyzed 53 53 19 26
Measure Type: Number
Unit of Measure: participants
9 9 1 1
3.Secondary Outcome
Title Phase II: Objective Response (Partial and Complete Response) Rate for Patients With Measurable Disease After Surgery
Hide Description Response and progression will be evaluated using standard criteria for patients with malignant gliomas (Macdonald 1990). Partial response and complete response are centrally reviewed.
Time Frame Analysis occurs after all patients have been on study for at 6 months. (Patients are followed from randomization to death or study termination whichever occurs first.)
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients with at least one cycle of treatment
Arm/Group Title Phase II: Arm 1/BEV-NAIVE Phase II: Arm 2/BEV-NAIVE Phase II: Arm 1/BEV-FAILURE Phase II: Arm 2/BEV-FAILURE
Hide Arm/Group Description:
ABT-888 40 mg x 5 days plus temozolomide 75 mg x 5 days
ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days
ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days
ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days
Overall Number of Participants Analyzed 53 53 19 26
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0
(0 to 0)
3.8
(0 to 8.9)
5.3
(0 to 15.3)
0
(0 to 0)
4.Secondary Outcome
Title Phase II: Overall Survival (OS)
Hide Description Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur when all patients had been potentially followed for at least 6 months.
Time Frame Analysis occurs after all patients have been on study for at 6 months. (Patients are followed from randomization to death or study termination whichever occurs first.)
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients
Arm/Group Title Phase II: Arm 1/BEV-NAIVE Phase II: Arm 2/BEV-NAIVE Phase II: Arm 1/BEV-FAILURE Phase II: Arm 2/BEV-FAILURE
Hide Arm/Group Description:
ABT-888 40 mg x 5 days plus temozolomide 75 mg x 5 days
ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days
ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days
ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days
Overall Number of Participants Analyzed 73 73 32 37
Median (95% Confidence Interval)
Unit of Measure: months
10.3
(7.6 to 13.4)
10.7
(7.6 to 12.6)
4.7
(3.0 to 6.3)
4.7
(3.4 to 7.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase II: Arm 1/BEV-NAIVE, Phase II: Arm 2/BEV-NAIVE
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.95
Comments [Not Specified]
Method Log Rank
Comments Two-sided test
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.66 to 1.48
Estimation Comments Reference level = Arm 1/BEV-NAIVE
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase II: Arm 1/BEV-FAILURE, Phase II: Arm 2/BEV-FAILURE
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.93
Comments [Not Specified]
Method Log Rank
Comments Two-sided test
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.57 to 1.53
Estimation Comments Reference level = Arm 1/BEV-FAILURE
Time Frame [Not Specified]
Adverse Event Reporting Description Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
 
Arm/Group Title Phase I: Dose Level 1 Phase I: Dose Level 2a Phase I: Dose Level 2b Phase I: Dose Level 3 Phase II: Arm 1/BEV-NAIVE Phase II: Arm 2/BEV-NAIVE Phase II: Arm 1/BEV-FAILURE Phase II: Arm 2/BEV-FAILURE
Hide Arm/Group Description ABT-888 20 mg x 21 days plus temozolomide 60 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 60 mg x 21 days ABT-888 20 mg x 21 days plus temozolomide 75 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days ABT-888 40 mg x 5 days plus temozolomide 75 mg x 5 days ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days
All-Cause Mortality
Phase I: Dose Level 1 Phase I: Dose Level 2a Phase I: Dose Level 2b Phase I: Dose Level 3 Phase II: Arm 1/BEV-NAIVE Phase II: Arm 2/BEV-NAIVE Phase II: Arm 1/BEV-FAILURE Phase II: Arm 2/BEV-FAILURE
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Phase I: Dose Level 1 Phase I: Dose Level 2a Phase I: Dose Level 2b Phase I: Dose Level 3 Phase II: Arm 1/BEV-NAIVE Phase II: Arm 2/BEV-NAIVE Phase II: Arm 1/BEV-FAILURE Phase II: Arm 2/BEV-FAILURE
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/8 (25.00%)   2/6 (33.33%)   1/9 (11.11%)   6/8 (75.00%)   19/73 (26.03%)   15/73 (20.55%)   14/32 (43.75%)   10/37 (27.03%) 
Blood and lymphatic system disorders                 
Anemia * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/73 (0.00%)  0/73 (0.00%)  1/32 (3.13%)  0/37 (0.00%) 
Cardiac disorders                 
Sinus tachycardia * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Gastrointestinal disorders                 
Colonic perforation * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Constipation * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  1/32 (3.13%)  0/37 (0.00%) 
Nausea * 1  0/8 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  1/8 (12.50%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Vomiting * 1  0/8 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  1/8 (12.50%)  0/73 (0.00%)  0/73 (0.00%)  1/32 (3.13%)  0/37 (0.00%) 
General disorders                 
Death NOS * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/73 (1.37%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Fatigue * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/73 (0.00%)  1/73 (1.37%)  1/32 (3.13%)  0/37 (0.00%) 
Non-cardiac chest pain * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Pain * 1  0/8 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Immune system disorders                 
Allergic reaction * 1  0/8 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/8 (0.00%)  1/73 (1.37%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Infections and infestations                 
Infections and infestations - Other * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/73 (1.37%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Lung infection * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/73 (1.37%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Meningitis * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Sepsis * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  1/32 (3.13%)  0/37 (0.00%) 
Skin infection * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/73 (1.37%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Urinary tract infection * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/73 (1.37%)  0/73 (0.00%)  1/32 (3.13%)  0/37 (0.00%) 
Wound infection * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  1/37 (2.70%) 
Injury, poisoning and procedural complications                 
Fall * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  2/37 (5.41%) 
Investigations                 
Creatinine increased * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Lymphocyte count decreased * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  2/8 (25.00%)  1/73 (1.37%)  1/73 (1.37%)  1/32 (3.13%)  1/37 (2.70%) 
Neutrophil count decreased * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  2/8 (25.00%)  5/73 (6.85%)  0/73 (0.00%)  1/32 (3.13%)  1/37 (2.70%) 
Platelet count decreased * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  3/73 (4.11%)  0/73 (0.00%)  5/32 (15.63%)  1/37 (2.70%) 
White blood cell decreased * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  2/8 (25.00%)  3/73 (4.11%)  0/73 (0.00%)  2/32 (6.25%)  0/37 (0.00%) 
Metabolism and nutrition disorders                 
Dehydration * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  2/32 (6.25%)  0/37 (0.00%) 
Hyperglycemia * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  1/32 (3.13%)  1/37 (2.70%) 
Hyponatremia * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  1/37 (2.70%) 
Hypophosphatemia * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  2/37 (5.41%) 
Musculoskeletal and connective tissue disorders                 
Generalized muscle weakness * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  2/32 (6.25%)  0/37 (0.00%) 
Muscle weakness left-sided * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Muscle weakness lower limb * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Muscle weakness right-sided * 1  0/8 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  3/73 (4.11%)  1/73 (1.37%)  6/32 (18.75%)  4/37 (10.81%) 
Nervous system disorders                 
Cognitive disturbance * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  1/37 (2.70%) 
Depressed level of consciousness * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  1/32 (3.13%)  0/37 (0.00%) 
Dysarthria * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Dysphasia * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  5/73 (6.85%)  0/32 (0.00%)  0/37 (0.00%) 
Edema cerebral * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/73 (1.37%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Encephalopathy * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  1/37 (2.70%) 
Facial muscle weakness * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Headache * 1  0/8 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  2/8 (25.00%)  0/73 (0.00%)  3/73 (4.11%)  0/32 (0.00%)  0/37 (0.00%) 
Intracranial hemorrhage * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  1/73 (1.37%)  2/73 (2.74%)  0/32 (0.00%)  0/37 (0.00%) 
Memory impairment * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Nervous system disorders - Other * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Peripheral motor neuropathy * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Seizure * 1  0/8 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  1/8 (12.50%)  5/73 (6.85%)  4/73 (5.48%)  0/32 (0.00%)  1/37 (2.70%) 
Somnolence * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Stroke * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  1/37 (2.70%) 
Syncope * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/73 (1.37%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Psychiatric disorders                 
Confusion * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Respiratory, thoracic and mediastinal disorders                 
Aspiration * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/73 (1.37%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Dyspnea * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Respiratory failure * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Vascular disorders                 
Hypotension * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  0/37 (0.00%) 
Thromboembolic event * 1  0/8 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  2/73 (2.74%)  3/73 (4.11%)  2/32 (6.25%)  0/37 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase I: Dose Level 1 Phase I: Dose Level 2a Phase I: Dose Level 2b Phase I: Dose Level 3 Phase II: Arm 1/BEV-NAIVE Phase II: Arm 2/BEV-NAIVE Phase II: Arm 1/BEV-FAILURE Phase II: Arm 2/BEV-FAILURE
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/8 (87.50%)   5/6 (83.33%)   9/9 (100.00%)   6/8 (75.00%)   70/73 (95.89%)   70/73 (95.89%)   31/32 (96.88%)   32/37 (86.49%) 
Blood and lymphatic system disorders                 
Anemia * 1  1/8 (12.50%)  2/6 (33.33%)  0/9 (0.00%)  3/8 (37.50%)  24/73 (32.88%)  25/73 (34.25%)  8/32 (25.00%)  11/37 (29.73%) 
Eye disorders                 
Vitreous hemorrhage * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Gastrointestinal disorders                 
Constipation * 1  1/8 (12.50%)  0/6 (0.00%)  4/9 (44.44%)  1/8 (12.50%)  20/73 (27.40%)  12/73 (16.44%)  11/32 (34.38%)  6/37 (16.22%) 
Dyspepsia * 1  1/8 (12.50%)  0/6 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  2/73 (2.74%)  3/73 (4.11%)  1/32 (3.13%)  0/37 (0.00%) 
Mucositis oral * 1  1/8 (12.50%)  1/6 (16.67%)  0/9 (0.00%)  0/8 (0.00%)  1/73 (1.37%)  2/73 (2.74%)  0/32 (0.00%)  1/37 (2.70%) 
Nausea * 1  1/8 (12.50%)  0/6 (0.00%)  1/9 (11.11%)  1/8 (12.50%)  19/73 (26.03%)  23/73 (31.51%)  8/32 (25.00%)  3/37 (8.11%) 
General disorders                 
Edema limbs * 1  1/8 (12.50%)  1/6 (16.67%)  0/9 (0.00%)  1/8 (12.50%)  4/73 (5.48%)  1/73 (1.37%)  1/32 (3.13%)  1/37 (2.70%) 
Fatigue * 1  1/8 (12.50%)  2/6 (33.33%)  5/9 (55.56%)  4/8 (50.00%)  36/73 (49.32%)  36/73 (49.32%)  16/32 (50.00%)  18/37 (48.65%) 
Pain * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  2/73 (2.74%)  4/73 (5.48%)  0/32 (0.00%)  0/37 (0.00%) 
Investigations                 
Alanine aminotransferase increased * 1  1/8 (12.50%)  0/6 (0.00%)  3/9 (33.33%)  4/8 (50.00%)  10/73 (13.70%)  16/73 (21.92%)  6/32 (18.75%)  3/37 (8.11%) 
Lymphocyte count decreased * 1  1/8 (12.50%)  1/6 (16.67%)  6/9 (66.67%)  3/8 (37.50%)  31/73 (42.47%)  31/73 (42.47%)  12/32 (37.50%)  13/37 (35.14%) 
Neutrophil count decreased * 1  1/8 (12.50%)  0/6 (0.00%)  2/9 (22.22%)  2/8 (25.00%)  25/73 (34.25%)  15/73 (20.55%)  7/32 (21.88%)  3/37 (8.11%) 
Platelet count decreased * 1  1/8 (12.50%)  1/6 (16.67%)  6/9 (66.67%)  3/8 (37.50%)  39/73 (53.42%)  48/73 (65.75%)  16/32 (50.00%)  22/37 (59.46%) 
White blood cell decreased * 1  1/8 (12.50%)  1/6 (16.67%)  4/9 (44.44%)  5/8 (62.50%)  32/73 (43.84%)  28/73 (38.36%)  11/32 (34.38%)  10/37 (27.03%) 
Metabolism and nutrition disorders                 
Hyperglycemia * 1  1/8 (12.50%)  2/6 (33.33%)  1/9 (11.11%)  3/8 (37.50%)  17/73 (23.29%)  18/73 (24.66%)  9/32 (28.13%)  10/37 (27.03%) 
Hypokalemia * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  4/73 (5.48%)  7/73 (9.59%)  3/32 (9.38%)  4/37 (10.81%) 
Musculoskeletal and connective tissue disorders                 
Muscle weakness left-sided * 1  1/8 (12.50%)  0/6 (0.00%)  1/9 (11.11%)  1/8 (12.50%)  4/73 (5.48%)  3/73 (4.11%)  4/32 (12.50%)  3/37 (8.11%) 
Muscle weakness lower limb * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  2/8 (25.00%)  2/73 (2.74%)  2/73 (2.74%)  5/32 (15.63%)  3/37 (8.11%) 
Nervous system disorders                 
Cognitive disturbance * 1  2/8 (25.00%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  6/73 (8.22%)  5/73 (6.85%)  2/32 (6.25%)  2/37 (5.41%) 
Dysarthria * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  5/73 (6.85%)  4/73 (5.48%)  2/32 (6.25%)  3/37 (8.11%) 
Headache * 1  2/8 (25.00%)  1/6 (16.67%)  5/9 (55.56%)  2/8 (25.00%)  28/73 (38.36%)  26/73 (35.62%)  10/32 (31.25%)  8/37 (21.62%) 
Hypersomnia * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  2/73 (2.74%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Lethargy * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  1/37 (2.70%) 
Memory impairment * 1  1/8 (12.50%)  1/6 (16.67%)  4/9 (44.44%)  0/8 (0.00%)  5/73 (6.85%)  12/73 (16.44%)  3/32 (9.38%)  3/37 (8.11%) 
Peripheral sensory neuropathy * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  1/73 (1.37%)  1/73 (1.37%)  2/32 (6.25%)  0/37 (0.00%) 
Seizure * 1  2/8 (25.00%)  1/6 (16.67%)  0/9 (0.00%)  1/8 (12.50%)  14/73 (19.18%)  10/73 (13.70%)  4/32 (12.50%)  4/37 (10.81%) 
Tremor * 1  1/8 (12.50%)  0/6 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  2/73 (2.74%)  7/73 (9.59%)  3/32 (9.38%)  1/37 (2.70%) 
Psychiatric disorders                 
Anxiety * 1  1/8 (12.50%)  1/6 (16.67%)  0/9 (0.00%)  0/8 (0.00%)  4/73 (5.48%)  5/73 (6.85%)  3/32 (9.38%)  3/37 (8.11%) 
Renal and urinary disorders                 
Urinary incontinence * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  2/8 (25.00%)  2/73 (2.74%)  2/73 (2.74%)  2/32 (6.25%)  2/37 (5.41%) 
Urinary tract pain * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  1/73 (1.37%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Respiratory, thoracic and mediastinal disorders                 
Cough * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/73 (1.37%)  6/73 (8.22%)  1/32 (3.13%)  1/37 (2.70%) 
Hypoxia * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/73 (0.00%)  0/73 (0.00%)  0/32 (0.00%)  0/37 (0.00%) 
Skin and subcutaneous tissue disorders                 
Rash acneiform * 1  1/8 (12.50%)  2/6 (33.33%)  1/9 (11.11%)  1/8 (12.50%)  2/73 (2.74%)  1/73 (1.37%)  2/32 (6.25%)  0/37 (0.00%) 
Skin ulceration * 1  1/8 (12.50%)  0/6 (0.00%)  0/9 (0.00%)  2/8 (25.00%)  0/73 (0.00%)  1/73 (1.37%)  0/32 (0.00%)  1/37 (2.70%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
[Not Specified]
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.
PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Wendy Seiferheld, M.S.
Organization: NRG Oncology
EMail: seiferheldw@nrgoncology.org
Layout table for additonal information
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT01026493    
Other Study ID Numbers: RTOG-0929
CDR0000660545
First Submitted: December 3, 2009
First Posted: December 4, 2009
Results First Submitted: January 17, 2017
Results First Posted: July 2, 2017
Last Update Posted: July 2, 2017