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Trial record 29 of 113 for:    Brain and Spinal Tumors

Erlotinib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Glioma

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ClinicalTrials.gov Identifier: NCT00124657
Recruitment Status : Completed
First Posted : July 28, 2005
Results First Posted : April 29, 2014
Last Update Posted : December 4, 2015
Sponsor:
Collaborators:
Rady Children's Hospital, San Diego
Duke University
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Brain and Central Nervous System Tumors
Intervention Drug: Erlotinib hydrochloride
Enrollment 62

Recruitment Details Overall accrual included 62 unique subjects. Five subjects participated in both Phase I and Phase II. Phase I enrolled 23 (03/2005-06/2007). Phase II enrolled an additional 39 participants (08/2007-11/2010) plus 5 carried over from Phase I for a total of 44. One of the 39 accrued to Phase II was enrolled at Rady Children's Hospital.
Pre-assignment Details Participants had newly diagnosed high-grade glioma (except those originating in the brain stem) and unfavorable low-grade glioma and were ≥ 3 and ≤21 years of age. Participants receiving enzyme-inducing anticonvulsants (EIACs) were not eligible for this study. Patients with spinal cord tumors were eligible for the Phase II component of this study.
Arm/Group Title Phase I Only Phase I and Phase II Phase II Only
Hide Arm/Group Description 18 participants were enrolled on the Phase I portion of the trial only. 5 patients participated in both the Phase I portion and the Phase II portion of the study. 39 participants were enrolled on the Phase II portion of the trial only.
Period Title: Overall Study
Started 18 5 39
Completed 2 0 7
Not Completed 16 5 32
Reason Not Completed
Toxicity             0             0             1
Non-compliance             1             0             4
Progressive disease             14             5             27
Intercurrent illness             1             0             0
Arm/Group Title Phase I Only Phase I and Phase II Phase II Only Total
Hide Arm/Group Description 18 participants were enrolled on the Phase I portion of the trial only. 5 patients participated in both the Phase I portion and the Phase II portion of the study. 39 participants were enrolled on the Phase II portion of the trial only. Total of all reporting groups
Overall Number of Baseline Participants 18 5 39 62
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 5 participants 39 participants 62 participants
11.49  (4.31) 11.47  (6.05) 10.55  (4.85) 11.12  (4.81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 5 participants 39 participants 62 participants
Female
8
  44.4%
2
  40.0%
23
  59.0%
33
  53.2%
Male
10
  55.6%
3
  60.0%
16
  41.0%
29
  46.8%
Diagnosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 18 participants 5 participants 39 participants 62 participants
Anaplastic astrocytoma (AA) 7 1 19 27
Glioblastoma multiforme (GBM) 8 4 17 29
Anaplastic oligoastrocytoma 2 0 1 3
Anaplastic ganglioglioma 1 0 0 1
Unfavorable fibrillary astrocytoma 0 0 1 1
Spinal GBM 0 0 1 1
1.Primary Outcome
Title Number of Participants With Dose-limiting Toxicity (DLT)
Hide Description DLT was defined as any of the following toxicities attributable to erlotinib therapy: thrombocytopenia grade 3 and 4; neutropenia grade 4; or any grade 3 and 4 non-hematologic toxicity except for grade 3 diarrhea and grade 3 nausea and vomiting lasting ≤48 hours in participants not receiving optimal supportive therapy, grade 3 skin rash, which did not affect normal daily activities, grade 3 fever or nonneutropenic infection, grade 3 seizures, grade 3 weight gain or loss, and grade 3 transaminase elevation that returned to grade 1 or baseline within 7 days. After enrollment of the first 4 participants, grade 3 and 4 electrolyte abnormalities that resolved to ≤grade 2 within 7 days were excluded as DLT. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0.
Time Frame During the first 8 weeks of therapy
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Hide Analysis Population Description
23 participants were enrolled on Phase I component; 22 were analyzed for DLT over 4 dose levels. 1 treated at dose level 120mg/m^2 was not assessable for DLT due to early tumor progression. 4 were treated before and 19 after the study was amended to exclude grade 3 and 4 electrolyte abnormalities that resolved to ≤ grade 2 within 7 days.
Arm/Group Title 70 mg/m^2 90 mg/m^2 120 mg/m^2 160 mg/m^2
Hide Arm/Group Description:
Dose level 1 was 70 mg/m^2, range of actual dosage was 68-83 mg/m^2.
Dose level 2 was 90 mg/m^2, range of actual dosage was 85-87.5 mg/m^2.
Dose level 3 was 120 mg/m^2, range of actual dosage was 107-128 mg/m^2.
Dose level 4 was 160 mg/m^2, range of actual dosage was 151.5-167 mg/m^2.
Overall Number of Participants Analyzed 7 3 6 6
Measure Type: Number
Unit of Measure: participants
0 0 1 2
2.Primary Outcome
Title Maximum Tolerated Dose (MTD) of Erlotinib
Hide Description MTD was defined as the highest dosage level in which no more than one of six assessable participants experienced dose-limiting toxicities (DLT). The dosage of erlotinib was increased by approximately 30% in each dosage level starting at 80% of the MTD in adults with solid tumors. A traditional 3+3 dose escalation scheme was used to estimate the MTD.
Time Frame During the first 8 weeks of therapy.
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Hide Analysis Population Description
22 participants were analyzed for MTD over 4 dose levels. One of 23 enrolled participants was not evaluable due to early disease progression.
Arm/Group Title Phase I
Hide Arm/Group Description:
22 participants were analyzed for MLT over 4 dose levels.
Overall Number of Participants Analyzed 22
Measure Type: Number
Unit of Measure: mg/m^2
120
3.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description

Progression-free survival (PFS) distributions for the Phase II participants with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) were calculated using Kaplan-Meier estimates (n=41). PFS was defined as the interval between treatment start and initial failure, including clinical or radiologic progression or death from any cause.

PFS was not calculated for the other disease types.

Time Frame 1 and 2 years after end of therapy
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Hide Analysis Population Description
Per protocol, 41 participants with either anaplastic astrocytoma or glioblastoma multiforme were analyzed for this outcome.
Arm/Group Title Phase I AA Phase I GBM Phase II AA Phase II GBM
Hide Arm/Group Description:
All participants with a diagnosis of anaplastic astrocytoma (AA) and treated on Phase I.
All participants with a diagnosis of glioblastoma multiforme (GBM) and treated on Phase I.
Participants with a diagnosis of intracranial anaplastic astrocytoma (AA) treated with a combination of maximum safe surgical resection, local RT, and erlotinib.
Participants with a diagnosis of intracranial glioblastoma multiforme (GBM) treated with a combination of maximum safe surgical resection, local RT, and erlotinib.
Overall Number of Participants Analyzed 8 12 20 21
Mean (Standard Deviation)
Unit of Measure: years
1-year PFS 0.75  (0.14) 0.33  (0.12) 0.45  (0.106) 0.19  (0.077)
2-year PFS NA [1]   (NA) NA [1]   (NA) 0.15  (0.069) 0.19  (0.077)
[1]
2-year PFS was not done by diagnosis group for Phase I participants.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase I AA
Comments 1-year progression-free survival (n=8)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.48 to 1.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.14
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase I GBM
Comments 1-year progression-free survival (n=12)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.09 to 0.57
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Phase II AA
Comments 1-year progression free survival (n=20)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.198 to 0.602
Parameter Dispersion
Type: Standard Deviation
Value: 0.106
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Phase II AA
Comments 2-year progression free survival (n=20)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 0.150
Confidence Interval (2-Sided) 95%
0.015 to 0.285
Parameter Dispersion
Type: Standard Deviation
Value: 0.069
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Phase II GBM
Comments 1-year progression free survival (n=21)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 0.190
Confidence Interval (2-Sided) 95%
0.039 to 0.341
Parameter Dispersion
Type: Standard Deviation
Value: 0.077
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Phase II GBM
Comments 2-year progression free survival (n=21)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 0.190
Confidence Interval (2-Sided) 95%
0.039 to 0.341
Parameter Dispersion
Type: Standard Deviation
Value: 0.077
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Cmax of Erlotinib and Its Metabolite OSI-420
Hide Description Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose.
Time Frame After first dose of therapy, and Day 8 of therapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic variables were obtained in 17 patients enrolled on the Phase I portion of the study.
Arm/Group Title 70 mg/m^2 90 mg/m^2 120 mg/m^2 160 mg/m^2
Hide Arm/Group Description:
Dose level 1 was 70 mg/m^2, range of actual dosage was 68-83 mg/m^2.
Dose level 2 was 90 mg/m^2, range of actual dosage was 85-87.5 mg/m^2.
Dose level 3 was 120 mg/m^2, range of actual dosage was 107-128 mg/m^2.
Dose level 4 was 160 mg/m^2, range of actual dosage was 151.5-167 mg/m^2.
Overall Number of Participants Analyzed 7 2 5 3
Median (Full Range)
Unit of Measure: mg/mL
Erlotinib, after first dose of therapy
1.3
(0.94 to 2.2)
1.6
(1.3 to 1.8)
1.2
(0.5 to 2)
1.8
(1.3 to 3)
Erlotinib, Day 8 of therapy
1.8
(1.7 to 2.8)
1.3
(1.3 to 1.3)
1.4
(1 to 3)
2
(1.3 to 2.4)
OSI-420, after first dose of therapy
0.13
(0.05 to 0.2)
0.16
(0.12 to 0.2)
0.14
(0.1 to 0.3)
0.32
(0.26 to 0.33)
OSI-420, Day 8 of therapy
0.25
(0.2 to 0.6)
0.17
(0.17 to 0.17)
0.3
(0.1 to 0.5)
0.3
(0.3 to 0.3)
5.Secondary Outcome
Title Erlotinib Tmax
Hide Description Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose.
Time Frame After first dose of therapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic variables were obtained in 17 patients enrolled on the Phase I portion of the study.
Arm/Group Title 70 mg/m^2 90 mg/m^2 120 mg/m^2 160 mg/m^2
Hide Arm/Group Description:
Dose level 1 was 70 mg/m^2, range of actual dosage was 68-83 mg/m^2.
Dose level 2 was 90 mg/m^2, range of actual dosage was 85-87.5 mg/m^2.
Dose level 3 was 120 mg/m^2, range of actual dosage was 107-128 mg/m^2.
Dose level 4 was 160 mg/m^2, range of actual dosage was 151.5-167 mg/m^2.
Overall Number of Participants Analyzed 7 2 5 3
Median (Full Range)
Unit of Measure: hours
Erlotinib, after first dose of therapy
4
(2.1 to 8.2)
3.1
(2 to 4.1)
2.2
(1 to 4)
2.2
(2 to 2.5)
Erlotinib, Day 8 of therapy
2.1
(1 to 4.1)
2.6
(1.2 to 4)
1.75
(1.3 to 4)
2.2
(1 to 4)
6.Secondary Outcome
Title AUC Time 0-infinite (AUCinf) of Erlotinib and Its Metabolite OSI-420
Hide Description Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose.
Time Frame After first dose of therapy, and Day 8 of therapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic variables were obtained in 17 patients enrolled on the Phase I portion of the study.
Arm/Group Title 70 mg/m^2 90 mg/m^2 120 mg/m^2 160 mg/m^2
Hide Arm/Group Description:
Dose level 1 was 70 mg/m^2, range of actual dosage was 68-83 mg/m^2.
Dose level 2 was 90 mg/m^2, range of actual dosage was 85-87.5 mg/m^2.
Dose level 3 was 120 mg/m^2, range of actual dosage was 107-128 mg/m^2.
Dose level 4 was 160 mg/m^2, range of actual dosage was 151.5-167 mg/m^2.
Overall Number of Participants Analyzed 7 2 5 3
Median (Full Range)
Unit of Measure: mg*h/mL
Erlotinib, after first dose of therapy
34.9
(23.1 to 52.6)
23.9
(14.4 to 33.3)
27.8
(18.9 to 28.8)
37.1
(33.1 to 50.6)
Erlotinib, Day 8 of therapy
28.8
(21.8 to 30.9)
21.2
(18.1 to 24.2)
23.1
(11.8 to 51.2)
35.5
(23.7 to 51)
OSI-420, after first dose of therapy
2.1
(1.2 to 3.3)
1.9
(1.4 to 2.3)
2.5
(1.7 to 2.7)
4.2
(4.1 to 5.2)
OSI-420, Day 8 of therapy
3.3
(2 to 6.9)
2.1
(1.7 to 2.4)
2.8
(1.9 to 5.9)
4.3
(3.8 to 6.1)
7.Secondary Outcome
Title Number of Positive Mutations of EGFR and Downstream Pathways
Hide Description

Statistical analyses of genomic changes, expression profiles and validation studies should be considered in an exploratory and hypothesis-generating context.

Fresh frozen tumor tissue was obtained at the time of tumor resection and diagnosis. DNA was extracted from formalin-fixed, paraffin-embedded tissue. The entire PTEN coding sequence (exons 1-9), exons 1, 9 and 20 of PIK3CA, and exons 17-24 of EGFR were evaluated using exon-specific PCR amplification, and immunohistochemistry was done. Tumor lesions were considered positive if >25% cells were immunoreactive.

Time Frame Once at tumor resection and diagnosis
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Hide Analysis Population Description
Unstained slides were available for immunohistochemistry analysis in 21 of the 23 Phase I participants.
Arm/Group Title Phase I
Hide Arm/Group Description:
Phase I participants
Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: participants
Positive for PTEN (R130*) 1
Positive PIK3CA (H1047R) 1
Positive EGFR kinase domain 0
8.Secondary Outcome
Title Ability of Erlotinib to Inhibit EGFR Signaling
Hide Description

The objective was to test the ability of erlotinib to inhibit the EGFR signaling in patients with high-grade glioma who required a second surgery.

This outcome was not assessed due to insufficient availability of tumor and control samples for analysis.

Time Frame 5 Years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This outcome was not assessed due to insufficient availability of tumor and control samples for analysis.
Arm/Group Title Patients With High-Grade/Low-Grade Glioma
Hide Arm/Group Description:

Participants included patients with newly diagnosed high-grade glioma (excluding those originating in the brain stem) and unfavorable low-grade glioma who are ≥ 3 years and <26 years of age. Patients receiving enzyme-inducing anticonvulsants (EIACs) were not eligible for this study.

Patients received erlotinib hydrochloride: In the Phase II component of this study, erlotinib was given at the MTD during and after RT for 2 years. The recommended dose of erlotinib for the Phase II component of the current study was 120mg/m^2 per day (maximum dose of 200mg per day).

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Correlation Between Standard Magnetic Resonance Imaging and Investigational Radiologic Techniques in Assessing Tumor Response to This Treatment
Hide Description This objective was to prospectively investigate the correlation between standard magnetic resonance imaging (MRI) and investigational radiologic techniques (MR spectroscopy, perfusion/diffusion, PET scan, DEMRI/BLAST) in assessing tumor response to this treatment.
Time Frame at diagnosis and regular intervals during therapy (up to 2 years after start of therapy)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This objective became obsolete over the course of the protocol, and data was not collected.
Arm/Group Title Patients With High-Grade/Low-Grade Glioma
Hide Arm/Group Description:

Participants included patients with newly diagnosed high-grade glioma (excluding those originating in the brain stem) and unfavorable low-grade glioma who are ≥ 3 years and <26 years of age. Patients receiving enzyme-inducing anticonvulsants (EIACs) were not eligible for this study.

Patients received erlotinib hydrochloride: In the Phase II component of this study, erlotinib was given at the MTD during and after RT for 2 years. The recommended dose of erlotinib for the Phase II component of the current study was 120mg/m^2 per day (maximum dose of 200mg per day).

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title To Prospectively Investigate the Technical Factors Involved in Planning and Administering Conformal Fractionated RT as Outlined in This Study, and to Correlate RT Dosimetry With Patterns of Failure, Standard and Investigational Imaging and Toxicity
Hide Description [Not Specified]
Time Frame 5 Years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This objective became obsolete over the course of the protocol, and data was not collected.
Arm/Group Title Patients With High-Grade/Low-Grade Glioma
Hide Arm/Group Description:

Patients with newly diagnosed high-grade glioma (excluding those originating in the brain stem) and unfavorable low-grade glioma who are ≥ 3 years and <26 years of age. Patients receiving enzyme-inducing anticonvulsants (EIACs) are not eligible for this study. Patients with spinal cord tumors will be eligible for the Phase I and Phase II component of this study, but they will not be taken into consideration to estimate PFS in the Phase II component of this trial because of their notoriously worse prognosis. Patients receive erlotinib hydrochloride.

Erlotinib hydrochloride: This study had 2 components: a Phase I component which estimated the MTD and DLT(s) of erlotinib given once a day during and after conventionally fractionated RT for a period of 8 weeks (DLT-evaluation period), followed by continuous administration of this medication for up to 3 years; and a Phase II component where erlotinib was given at the MTD during and after RT for 2 years.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Plasma and CSF Levels of VEGF, bFGF, and SDF1
Hide Description This objective was to determine the plasma and CSF levels of the VEGF, bFGF, and SDF1 at diagnosis, and the plasma levels of these factors at regular intervals during therapy, and to analyze the association of these results with tumor response.
Time Frame at diagnosis and regular intervals during therapy (up to 2 years after start of therapy)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This objective became obsolete over the course of the protocol, and data was not collected.
Arm/Group Title Patients With High-Grade/Low-Grade Glioma
Hide Arm/Group Description:

Participants included patients with newly diagnosed high-grade glioma (excluding those originating in the brain stem) and unfavorable low-grade glioma who are ≥ 3 years and <26 years of age. Patients receiving enzyme-inducing anticonvulsants (EIACs) were not eligible for this study.

Patients received erlotinib hydrochloride: In the Phase II component of this study, erlotinib was given at the MTD during and after RT for 2 years. The recommended dose of erlotinib for the Phase II component of the current study was 120mg/m^2 per day (maximum dose of 200mg per day).

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Number of Participants Experiencing Grade 3 or 4 Toxicity Events
Hide Description Adverse events were collected systematically for each of the 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Time Frame From start of therapy through 2 years.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All 44 Phase II participants were evaluated. Eight of 16 participants with lymphopenia received dexamethasone within 4 weeks of the recorded toxicity. In both participants with headache, there was a documented progressive disease within 3 days of the recorded headache.
Arm/Group Title Grade 3 Toxicity Grade 4 Toxicity
Hide Arm/Group Description:
Grade 3 toxicity per CTCAE 3.0.
Grade 4 toxicity per CTCAE 3.0.
Overall Number of Participants Analyzed 44 44
Measure Type: Number
Unit of Measure: Participants
Blood: Hemoglobin 2 1
Blood: Lymphopenia 7 8
Blood: Neutrophils 2 1
Blood: Platelets 0 1
Dermatologic: Pruritus 3 0
Dermatologic: Rash/Desquamation 1 0
Dermatologic: Rash/acne 2 0
Gastrointestinal: Anorexia 3 0
Gastrointestinal: Diarrhea 5 0
Gastrointestinal: Dysphagia 1 0
Gastrointestinal: Mucositis 1 0
Gastrointestinal: Nausea 2 0
Gastrointestinal: Vomiting 4 0
Metabolic: ALT/AST 2 0
Metabolic: Hypokalemia 2 0
Metabolic: Bilirubin 1 0
Pain: Headache 1 1
Constitutional: Fatigue 1 0
Constitutional: Weight Loss 2 0
Time Frame Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 70 mg/m^2 (Phase I) 90 mg/m^2 (Phase I) 120 mg/m^2 (Phase I) 160 mg/m^2 (Phase I) Phase II
Hide Arm/Group Description Participants received dose of 70 mg/m^2, range of actual dose was 68-83 mg/m^2. Participants received dose of 90 mg/m^2, range of actual dose was 85-87.5 mg/m^2. Participants received dose of 120 mg/m^2, range of actual dose was 107-128 mg/m^2. Participants received dose of 160 mg/m^2, range of actual dose was 151.5-167 mg/m^2. Phase II participants received 120 mg/m^2.
All-Cause Mortality
70 mg/m^2 (Phase I) 90 mg/m^2 (Phase I) 120 mg/m^2 (Phase I) 160 mg/m^2 (Phase I) Phase II
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
70 mg/m^2 (Phase I) 90 mg/m^2 (Phase I) 120 mg/m^2 (Phase I) 160 mg/m^2 (Phase I) Phase II
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/7 (57.14%)      1/3 (33.33%)      2/7 (28.57%)      4/6 (66.67%)      26/44 (59.09%)    
Blood and lymphatic system disorders           
Hemoglobin * 1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 3/44 (6.82%)  7
Lymphopenia  1 [1]  2/7 (28.57%)  2 1/3 (33.33%)  1 2/7 (28.57%)  2 4/6 (66.67%)  6 16/44 (36.36%)  32
Neutrophils  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 3/44 (6.82%)  3
Platelets  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/44 (2.27%)  1
Gastrointestinal disorders           
Anorexia  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 3/44 (6.82%)  4
Diarrhea  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 5/44 (11.36%)  6
Dysphagia  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/44 (2.27%)  1
Mucositis  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/44 (2.27%)  1
Nausea  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  2
Vomiting  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 4/44 (9.09%)  4
General disorders           
Fatigue  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/44 (2.27%)  1
Weight loss  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  2
Headache  1 [2]  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  2
Metabolism and nutrition disorders           
ALT/AST  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  2
Hypokalemia  1  2/7 (28.57%)  2 0/3 (0.00%)  0 1/7 (14.29%)  2 0/6 (0.00%)  0 2/44 (4.55%)  4
Bilirubin  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/44 (2.27%)  1
Lipase  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/44 (0.00%)  0
Hypophosphatemia  1  1/7 (14.29%)  1 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Skin and subcutaneous tissue disorders           
Pruritis  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 3/44 (6.82%)  4
Rash/Desquamation  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/44 (2.27%)  1
Rash/Acne  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  2
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Eight of the 16 patients with lymphopenia received dexamethasone within 4 weeks of the recorded toxicity.
[2]
There was a documented progressive disease within 3 days of the recorded headache.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
70 mg/m^2 (Phase I) 90 mg/m^2 (Phase I) 120 mg/m^2 (Phase I) 160 mg/m^2 (Phase I) Phase II
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/7 (100.00%)      3/3 (100.00%)      7/7 (100.00%)      6/6 (100.00%)      43/44 (97.73%)    
Blood and lymphatic system disorders           
Hemoglobin  1  6/7 (85.71%)  15 2/3 (66.67%)  2 3/7 (42.86%)  3 4/6 (66.67%)  7 18/44 (40.91%)  41
Leukocytes (total WBC)  1  4/7 (57.14%)  10 2/3 (66.67%)  3 5/7 (71.43%)  6 3/6 (50.00%)  8 21/44 (47.73%)  38
Lymphopenia  1  7/7 (100.00%)  18 3/3 (100.00%)  8 7/7 (100.00%)  14 6/6 (100.00%)  13 27/44 (61.36%)  104
Neutrophils/granulocytes (ANC/AGC)  1  2/7 (28.57%)  6 1/3 (33.33%)  1 1/7 (14.29%)  1 1/6 (16.67%)  1 10/44 (22.73%)  16
Platelets  1  2/7 (28.57%)  2 0/3 (0.00%)  0 2/7 (28.57%)  3 3/6 (50.00%)  5 8/44 (18.18%)  10
Edema: limb  1  1/7 (14.29%)  1 1/3 (33.33%)  1 0/7 (0.00%)  0 1/6 (16.67%)  1 4/44 (9.09%)  4
Lymphatics - other  1  0/7 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Cardiac disorders           
Supraventricular and nodal arrhythmia, sinus tachycardia  1  0/7 (0.00%)  0 1/3 (33.33%)  1 1/7 (14.29%)  1 2/6 (33.33%)  4 3/44 (6.82%)  4
Hypertension  1  3/7 (42.86%)  4 2/3 (66.67%)  2 2/7 (28.57%)  2 1/6 (16.67%)  1 6/44 (13.64%)  7
Hypotension  1  0/7 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 3/44 (6.82%)  3
Supraventricular and nodal arrhythmia, sinus bradycardia  1  0/7 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Palpitations  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  3
Ear and labyrinth disorders           
Hearing: patients wihtout baseline audiogram and not enrolled in a monitoring program  1  1/7 (14.29%)  1 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 3/44 (6.82%)  4
Otitis, external ear (non-infectious)  1  1/7 (14.29%)  4 2/3 (66.67%)  4 1/7 (14.29%)  1 0/6 (0.00%)  0 5/44 (11.36%)  6
Auditory/Ear - other * 1  5/7 (71.43%)  8 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  2
Otitis, middle ear (non-infectious  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/44 (2.27%)  1
Tinnitus  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 2/44 (4.55%)  2
Endocrine disorders           
Cushingoid appearance(e.g. moon face, buffalo hump, centripetal obesity, cutaneous striae)  1  2/7 (28.57%)  2 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 5/44 (11.36%)  5
Eye disorders           
Nystagmus  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 3/44 (6.82%)  3
Ocular/visual - other  1  2/7 (28.57%)  2 1/3 (33.33%)  1 0/7 (0.00%)  0 1/6 (16.67%)  1 10/44 (22.73%)  11
Ophthalmoplegia/diplopia (double vision)  1  2/7 (28.57%)  2 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 4/44 (9.09%)  5
Vision-blurred vision  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 3/44 (6.82%)  3
Ocular surface disease  1  1/7 (14.29%)  1 1/3 (33.33%)  1 2/7 (28.57%)  2 4/6 (66.67%)  4 2/44 (4.55%)  2
Vision-photophobia  1  2/7 (28.57%)  2 1/3 (33.33%)  1 1/7 (14.29%)  1 0/6 (0.00%)  0 1/44 (2.27%)  1
Cataract  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Dry eye syndrome  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/44 (2.27%)  1
Eyelid dysfunction  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Gastrointestinal disorders           
Anorexia  1  4/7 (57.14%)  10 2/3 (66.67%)  3 2/7 (28.57%)  3 5/6 (83.33%)  5 26/44 (59.09%)  30
Constipation  1  3/7 (42.86%)  4 1/3 (33.33%)  1 1/7 (14.29%)  1 4/6 (66.67%)  4 8/44 (18.18%)  11
Dehydration  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  2 7/44 (15.91%)  7
Diarrhea  1  6/7 (85.71%)  13 3/3 (100.00%)  4 7/7 (100.00%)  8 4/6 (66.67%)  8 28/44 (63.64%)  51
Gastrointestinal - Other  1  1/7 (14.29%)  2 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 8/44 (18.18%)  12
Heartburn/dyspepsia  1  1/7 (14.29%)  2 2/3 (66.67%)  3 0/7 (0.00%)  0 0/6 (0.00%)  0 5/44 (11.36%)  5
Mucositis/stomatitis (clinical exam), oral cavity  1  1/7 (14.29%)  1 3/3 (100.00%)  5 3/7 (42.86%)  3 1/6 (16.67%)  1 4/44 (9.09%)  4
Mucositis/stomatitis (functional/symptomatic), oral cavity  1  1/7 (14.29%)  1 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 3/44 (6.82%)  3
Nausea  1  6/7 (85.71%)  11 2/3 (66.67%)  5 3/7 (42.86%)  4 4/6 (66.67%)  6 19/44 (43.18%)  27
Taste alteration (dysgeusia)  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 5/44 (11.36%)  7
Vomiting  1  5/7 (71.43%)  13 1/3 (33.33%)  3 3/7 (42.86%)  4 4/6 (66.67%)  5 19/44 (43.18%)  31
Dental: teeth  1  1/7 (14.29%)  1 1/3 (33.33%)  1 1/7 (14.29%)  1 1/6 (16.67%)  1 0/44 (0.00%)  0
Dysphagia (difficulty swallowing)  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/44 (2.27%)  1
Flatulence  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Gastritis (including bile reflex gastritis)  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 1/44 (2.27%)  1
Ulcer, GI, stomach  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/44 (0.00%)  0
General disorders           
Fatigue (asthenia, lethargy, malaise)  1  5/7 (71.43%)  8 0/3 (0.00%)  0 2/7 (28.57%)  3 3/6 (50.00%)  4 18/44 (40.91%)  25
Fever (in absence of neutrophenia defined as ANC <1.0 x 10e9/L)  1  5/7 (71.43%)  8 1/3 (33.33%)  1 2/7 (28.57%)  2 1/6 (16.67%)  1 8/44 (18.18%)  10
Insomnia  1  1/7 (14.29%)  3 2/3 (66.67%)  2 1/7 (14.29%)  1 0/6 (0.00%)  0 3/44 (6.82%)  3
Weight loss  1  3/7 (42.86%)  4 0/3 (0.00%)  0 1/7 (14.29%)  1 2/6 (33.33%)  4 19/44 (43.18%)  27
Pain - other  1  1/7 (14.29%)  1 0/3 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  1 11/44 (25.00%)  17
Pain, abdomen NOS  1  3/7 (42.86%)  3 1/3 (33.33%)  1 1/7 (14.29%)  1 2/6 (33.33%)  3 6/44 (13.64%)  7
Pain, back  1  1/7 (14.29%)  2 1/3 (33.33%)  2 2/7 (28.57%)  2 1/6 (16.67%)  1 4/44 (9.09%)  5
Pain, head/headache  1  5/7 (71.43%)  17 2/3 (66.67%)  3 3/7 (42.86%)  4 5/6 (83.33%)  6 20/44 (45.45%)  29
Pain, throat/pharynx/larynx  1  0/7 (0.00%)  0 1/3 (33.33%)  1 1/7 (14.29%)  1 0/6 (0.00%)  0 7/44 (15.91%)  7
Rigors/chills  1  2/7 (28.57%)  2 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  2
Pain, chest/thorax NOS  1  0/7 (0.00%)  0 2/3 (66.67%)  3 0/7 (0.00%)  0 1/6 (16.67%)  1 1/44 (2.27%)  1
Pain, external ear  1  0/7 (0.00%)  0 2/3 (66.67%)  2 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Pain, eye  1  1/7 (14.29%)  1 0/3 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  1 1/44 (2.27%)  1
Pain, joint  1  2/7 (28.57%)  2 1/3 (33.33%)  1 0/7 (0.00%)  0 2/6 (33.33%)  2 1/44 (2.27%)  1
Weight gain  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/44 (0.00%)  0
Flu-like syndrome  1  0/7 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Pain, extremity-limb  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/44 (0.00%)  0
Pain, muscle  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Pain, oral cavity  1  1/7 (14.29%)  2 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  2
Pain, pain NOS  1  0/7 (0.00%)  0 1/3 (33.33%)  2 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Pain, stomach  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 2/44 (4.55%)  2
Hepatobiliary disorders           
Hepatobiliary/pancreas - other  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Immune system disorders           
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip) * 1  3/7 (42.86%)  3 0/3 (0.00%)  0 2/7 (28.57%)  2 3/6 (50.00%)  3 8/44 (18.18%)  11
Allergic reaction/hypersensitivity (including drug fever)  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/44 (2.27%)  1
Infections and infestations           
Infection - Other  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  3 19/44 (43.18%)  26
Infection with normal ANC or Grade 1 or 2 neurophils, external ear (otitis externa)  1  3/7 (42.86%)  3 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 3/44 (6.82%)  3
Infection with normal ANC or Grade 1 or 2 neutrophils, middle ear (otitis media) * 1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 3/44 (6.82%)  3
Infection with normal ANC or Grade 1 or 2 neutrophils, upper airway NOS  1  0/7 (0.00%)  0 2/3 (66.67%)  2 1/7 (14.29%)  1 2/6 (33.33%)  2 3/44 (6.82%)  3
Opportunistic infection associated with >=Grade 2 lymphopenia  1  1/7 (14.29%)  1 0/3 (0.00%)  0 1/7 (14.29%)  2 2/6 (33.33%)  3 5/44 (11.36%)  6
Infection with normal ANC or Grade 1 or 2 neutrophils, Anal/perianal  1  1/7 (14.29%)  1 1/3 (33.33%)  2 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils, eye NOS  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  1 0/44 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils, mucosa  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  1 1/44 (2.27%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils, pharynx  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  1 1/44 (2.27%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils, sinus  1  0/7 (0.00%)  0 1/3 (33.33%)  1 1/7 (14.29%)  1 0/6 (0.00%)  0 1/44 (2.27%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils, skin (cellulitis)  1  1/7 (14.29%)  1 1/3 (33.33%)  1 0/7 (0.00%)  0 1/6 (16.67%)  1 0/44 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils, urinary tract NOS  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 2/6 (33.33%)  2 1/44 (2.27%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils, wound  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 3/6 (50.00%)  3 2/44 (4.55%)  3
Infection with normal ANC or Grade 1 or 2 neutrophils, lip/perioral  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 2/6 (33.33%)  2 0/44 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils, conjunctiva  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 1/44 (2.27%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils, dental-tooth  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 1/44 (2.27%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils, Foreign body  1 [1]  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils, lung (pnemonia)  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/44 (2.27%)  2
Infection with normal ANC or Grade 1 or 2 neutrophils, meninges (meningitis)  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils, nose  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 1/44 (2.27%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils, oral cavity-gums (gingivitis)  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/44 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils, rectum  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/44 (0.00%)  0
Injury, poisoning and procedural complications           
Death not associated with CTCAE term, disease progression NOS  1 [2]  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/44 (0.00%)  0
Intra-operative injury, brain  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/44 (0.00%)  0
Metabolism and nutrition disorders           
ALT, SGPT (serum glutamic pyruvic transaminase)  1  2/7 (28.57%)  2 3/3 (100.00%)  6 3/7 (42.86%)  3 2/6 (33.33%)  6 14/44 (31.82%)  26
AST, SGOT (serum glutamic oxaloacetic transaminase)  1  1/7 (14.29%)  1 2/3 (66.67%)  3 1/7 (14.29%)  1 2/6 (33.33%)  5 13/44 (29.55%)  20
Albumin, serum-low (hypoalbuminemia)  1  4/7 (57.14%)  5 0/3 (0.00%)  0 2/7 (28.57%)  2 1/6 (16.67%)  1 11/44 (25.00%)  19
Alkaline phosphatase  1  0/7 (0.00%)  0 2/3 (66.67%)  2 0/7 (0.00%)  0 0/6 (0.00%)  0 4/44 (9.09%)  6
Bicarbonate, serum-low  1  1/7 (14.29%)  2 0/3 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  1 5/44 (11.36%)  5
Bilirubin (hyperbilirubinemia)  1  0/7 (0.00%)  0 2/3 (66.67%)  5 4/7 (57.14%)  8 2/6 (33.33%)  5 16/44 (36.36%)  25
Calcium, serum-low (hypocalcemia)  1  4/7 (57.14%)  4 2/3 (66.67%)  2 1/7 (14.29%)  1 1/6 (16.67%)  2 7/44 (15.91%)  12
Creatinine  1  0/7 (0.00%)  0 1/3 (33.33%)  1 1/7 (14.29%)  3 0/6 (0.00%)  0 4/44 (9.09%)  7
Glucose, serum-high (hyperglycemia)  1  6/7 (85.71%)  13 2/3 (66.67%)  2 1/7 (14.29%)  1 3/6 (50.00%)  5 13/44 (29.55%)  23
Glucose, serum-low (hypoglycemia)  1  0/7 (0.00%)  0 1/3 (33.33%)  1 2/7 (28.57%)  2 1/6 (16.67%)  3 8/44 (18.18%)  14
Magnesium, serum-high (hypermagnesemia)  1  1/7 (14.29%)  1 0/3 (0.00%)  0 6/7 (85.71%)  13 4/6 (66.67%)  5 9/44 (20.45%)  15
Phosphate, serum-low (hypophosphatemia)  1  6/7 (85.71%)  10 2/3 (66.67%)  7 2/7 (28.57%)  3 4/6 (66.67%)  5 12/44 (27.27%)  22
Potassium, serum-low (hypokalemia)  1  5/7 (71.43%)  10 0/3 (0.00%)  0 2/7 (28.57%)  3 3/6 (50.00%)  5 12/44 (27.27%)  23
Potassium, serum-high (hyperkalemia)  1  1/7 (14.29%)  1 1/3 (33.33%)  2 0/7 (0.00%)  0 1/6 (16.67%)  1 3/44 (6.82%)  4
Sodium, serum-high (hypernatremia)  1  0/7 (0.00%)  0 1/3 (33.33%)  2 4/7 (57.14%)  10 1/6 (16.67%)  4 15/44 (34.09%)  28
Sodium, serum-low (hyponatremia)  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 3/44 (6.82%)  6
Calcium, serum-high (hypercalcemia)  1  1/7 (14.29%)  1 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/44 (0.00%)  0
Magnesium, serum-low (hypomagnesemia)  1  0/7 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 1/6 (16.67%)  2 1/44 (2.27%)  1
Amylase  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/44 (2.27%)  1
Cholesterol, serum-high (hypercholestremia)  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Lipase  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/44 (2.27%)  1
Metabolic/laboratory - other  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Musculoskeletal/soft tissue - other  1  1/7 (14.29%)  2 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 3/44 (6.82%)  4
Extremity-lower (gait/walking)  1  3/7 (42.86%)  3 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  2
Muscle weakness, generalized or specific area (not due to neuropathy), whole body/generalized  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/44 (2.27%)  1
Trismus (difficulty, restriction or pain when opening mouth)  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Secondary malignancy - possibly related to cancer treatment  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/44 (0.00%)  0
Nervous system disorders           
Ataxia (incoordination)  1  2/7 (28.57%)  2 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 8/44 (18.18%)  13
Dizziness  1  1/7 (14.29%)  1 1/3 (33.33%)  1 1/7 (14.29%)  1 1/6 (16.67%)  2 3/44 (6.82%)  3
Mood alteration, anxiety  1  1/7 (14.29%)  2 0/3 (0.00%)  0 2/7 (28.57%)  2 0/6 (0.00%)  0 5/44 (11.36%)  5
Mood alteration, depression  1  0/7 (0.00%)  0 2/3 (66.67%)  3 0/7 (0.00%)  0 3/6 (50.00%)  3 6/44 (13.64%)  8
Neurology - other  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 8/44 (18.18%)  12
Neuropathy: motor  1  3/7 (42.86%)  7 0/3 (0.00%)  0 3/7 (42.86%)  3 4/6 (66.67%)  4 4/44 (9.09%)  6
Seizure  1  3/7 (42.86%)  4 1/3 (33.33%)  1 4/7 (57.14%)  4 3/6 (50.00%)  3 11/44 (25.00%)  25
Speech impairment (e.g., dysphasia or aphasia)  1  2/7 (28.57%)  3 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 3/44 (6.82%)  3
Tremor  1  0/7 (0.00%)  0 1/3 (33.33%)  1 2/7 (28.57%)  2 1/6 (16.67%)  1 3/44 (6.82%)  3
Cognitive disturbance  1  1/7 (14.29%)  1 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Memory impairment  1  2/7 (28.57%)  2 1/3 (33.33%)  1 1/7 (14.29%)  1 0/6 (0.00%)  0 2/44 (4.55%)  2
Personality/behavioral  1  0/7 (0.00%)  0 1/3 (33.33%)  1 2/7 (28.57%)  2 0/6 (0.00%)  0 2/44 (4.55%)  2
Somnolence/depressed level of consciousness  1  1/7 (14.29%)  2 0/3 (0.00%)  0 0/7 (0.00%)  0 2/6 (33.33%)  2 0/44 (0.00%)  0
Syncope (fainting)  1  1/7 (14.29%)  1 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Hydrocephalus  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/44 (2.27%)  1
Leak, cerebrospinal fluid (CSF)  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Mood alteration, agitation  1  0/7 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 1/44 (2.27%)  1
Neuropathy: cranial, CN VI Lateral deviation of eye  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/44 (2.27%)  1
Neuropathy: cranial, CN VII motor-face: sensory-taste  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/44 (0.00%)  0
Neuropathy: cranial, CN VIII hearing and balance  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/44 (2.27%)  1
Neuropathy: sensory  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  2
Psychosis (hallucinations/delusions)  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Pyramidal tract dysfunction  1 [3]  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 1/44 (2.27%)  1
Renal and urinary disorders           
Urinary retention (including neurogenic bladder)  1  1/7 (14.29%)  1 0/3 (0.00%)  0 2/7 (28.57%)  2 0/6 (0.00%)  0 2/44 (4.55%)  2
Cystitis  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 1/44 (2.27%)  1
Urinary frequency/urgency  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  3
Reproductive system and breast disorders           
Sexual/reproductive function - other  1  0/7 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Cough  1  6/7 (85.71%)  8 2/3 (66.67%)  2 1/7 (14.29%)  1 2/6 (33.33%)  4 7/44 (15.91%)  7
Dyspnea (shortness of breath)  1  2/7 (28.57%)  3 1/3 (33.33%)  1 1/7 (14.29%)  2 0/6 (0.00%)  0 2/44 (4.55%)  3
Nasal cavity/paranasal sinus reactions  1  4/7 (57.14%)  9 1/3 (33.33%)  1 1/7 (14.29%)  1 1/6 (16.67%)  1 1/44 (2.27%)  1
Bronchospasm, wheezing  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Pulmonary/upper respiratory - other  1  1/7 (14.29%)  2 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Skin and subcutaneous tissue disorders           
Chelitis  1  1/7 (14.29%)  2 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 3/44 (6.82%)  3
Dermatology/Skin - other  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 8/44 (18.18%)  14
Dry skin  1  4/7 (57.14%)  6 2/3 (66.67%)  2 2/7 (28.57%)  2 4/6 (66.67%)  5 18/44 (40.91%)  19
Hair loss/alopecia (scalp or body)  1  6/7 (85.71%)  6 2/3 (66.67%)  2 2/7 (28.57%)  3 1/6 (16.67%)  1 13/44 (29.55%)  14
Hyperpigmentation  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 3/44 (6.82%)  3
Nail changes  1  2/7 (28.57%)  2 1/3 (33.33%)  1 3/7 (42.86%)  3 4/6 (66.67%)  4 7/44 (15.91%)  7
Pruritus/itching  1  3/7 (42.86%)  3 1/3 (33.33%)  1 2/7 (28.57%)  3 1/6 (16.67%)  1 16/44 (36.36%)  21
Rash/desquamation  1  5/7 (71.43%)  6 2/3 (66.67%)  2 4/7 (57.14%)  5 3/6 (50.00%)  4 19/44 (43.18%)  27
Rash: acne/acneiform  1  6/7 (85.71%)  8 3/3 (100.00%)  4 5/7 (71.43%)  5 2/6 (33.33%)  2 18/44 (40.91%)  29
Striae  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 2/6 (33.33%)  2 3/44 (6.82%)  3
Flushing  1  2/7 (28.57%)  3 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Rash: hand-foot skin reaction  1  2/7 (28.57%)  2 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Ulceration  1  0/7 (0.00%)  0 3/3 (100.00%)  4 1/7 (14.29%)  1 0/6 (0.00%)  0 1/44 (2.27%)  1
Bruising (in absence of Grade 3 or 4 thrombocytopenia)  1  0/7 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 2/44 (4.55%)  3
Burn  1  1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/44 (0.00%)  0
Rash: dermatitis associated with radiation, radiation  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 1/44 (2.27%)  1
Vascular disorders           
Hemorrhage, pulmonary/upper respiratory, nose  1  1/7 (14.29%)  1 1/3 (33.33%)  1 2/7 (28.57%)  2 1/6 (16.67%)  1 4/44 (9.09%)  6
Hemorrhage, CNS  1  0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 2/6 (33.33%)  2 0/44 (0.00%)  0
Hemorrhage, GU, urinary NOS  1  0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  1 1/44 (2.27%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
e.g., graft, implant, prosthesis, stent
[2]
Death occurred due to a sledding accident. Participant had completed all therapy and was in follow-up.
[3]
(e.g., increased tone, hyperreflexia, positive Babinski, decreased motor coordination)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Alberto Broniscer, MD
Organization: St. Jude Children's Research Hospital
Phone: 866-966-5934
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00124657     History of Changes
Other Study ID Numbers: SJHG04
First Submitted: July 26, 2005
First Posted: July 28, 2005
Results First Submitted: September 10, 2013
Results First Posted: April 29, 2014
Last Update Posted: December 4, 2015