Trial · NCT01514201

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

NCT01514201, Phase 1, Phase 2, Completed, National Cancer Institute (NCI); results first posted 2019-08-13

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas. Trials, record NCT01514201. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01514201

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas
NCT number: NCT01514201
Status: Completed
Phases: Phase 1, Phase 2
Enrollment: 66 participants, actual
Lead sponsor: National Cancer Institute (NCI)
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: 3-Dimensional Conformal Radiation Therapy, Intensity-Modulated Radiation Therapy, Laboratory Biomarker Analysis, Pharmacological Study, Temozolomide, Veliparib
First posted: 2012-01-23
Last updated: 2019-08-13
Results first posted: 2019-08-13

Source ClinicalTrials.gov

Registered outcomes16

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	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)	10 weeks	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.
Primary	Percentage of Participants Observed to Have Unacceptable Toxicity During the Intra-patient Dose Escalation of Temozolomide During Maintenance Therapy (Feasibility Analysis Population)	28 days per treatment cycle	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.
Primary	Overall Survival	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	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.
Primary	Number of Phase I Patients Who Experienced Dose Limiting Toxicities (DLTs)	10 weeks	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.
Secondary	Progression-free Survival (PFS)	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	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.
Secondary	Percentage of Patients With Pseudo Progression	Up to 6 months	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.
Secondary	Maximum Concentration of Veliparib (Cmax) on Days 1 and 4 (Measured in ng/mL) [Pharmacokinetic Parameter]	Up to day 4	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.
Secondary	Mean Apparent Clearance (CL/F) for Veliparib [Pharmacokinetic Parameter]	Up to day 4	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.
Secondary	Maximum Concentration of Veliparib (Cmax) on Day 1 (Measured in μM) [Pharmacokinetic Parameter]	Day 1	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.
Secondary	Apparent Volume of Distribution (Vd/F) for Veliparib [Pharmacokinetic Parameter]	Up to day 4	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.

1 to 10 of 16Source ClinicalTrials.gov

See all 16 registered outcomes

Outcomes16

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	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)	10 weeks	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.	mg/m2/dose BID	NUMBER
PRIMARY	Percentage of Participants Observed to Have Unacceptable Toxicity During the Intra-patient Dose Escalation of Temozolomide During Maintenance Therapy (Feasibility Analysis Population)	28 days per treatment cycle	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.	% of participants	NUMBER
PRIMARY	Overall Survival	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	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.	Percent probability	NUMBER
PRIMARY	Number of Phase I Patients Who Experienced Dose Limiting Toxicities (DLTs)	10 weeks		Participants	COUNT_OF_PARTICIPANTS
SECONDARY	Progression-free Survival (PFS)	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	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.	Percent probability	NUMBER
SECONDARY	Percentage of Patients With Pseudo Progression	Up to 6 months		Percentage of participants	NUMBER
SECONDARY	Maximum Concentration of Veliparib (Cmax) on Days 1 and 4 (Measured in ng/mL) [Pharmacokinetic Parameter]	Up to day 4	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.	ng/mL	MEAN
SECONDARY	Mean Apparent Clearance (CL/F) for Veliparib [Pharmacokinetic Parameter]	Up to day 4	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.	L/m^2/h	MEAN
SECONDARY	Maximum Concentration of Veliparib (Cmax) on Day 1 (Measured in μM) [Pharmacokinetic Parameter]	Day 1	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.	μM	MEAN
OTHER_PRE_SPECIFIED	Percentage of Participants With Significant Changes in Poly(ADP-ribose) Polymerase (PARP) Levels Post-Veliparib, as Measured in Peripheral Blood Monocytes (PBMCs)	Baseline and up to 11 weeks	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.	percentage of participants	NUMBER

1 to 10 of 16Source ClinicalTrials.gov

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Results by group109

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
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)	Phase I Patients	65		mg/m2/dose BID
Percentage of Participants Observed to Have Unacceptable Toxicity During the Intra-patient Dose Escalation of Temozolomide During Maintenance Therapy (Feasibility Analysis Population)	Dose Level 1 (135 mg/m2)	9		% of participants
Percentage of Participants Observed to Have Unacceptable Toxicity During the Intra-patient Dose Escalation of Temozolomide During Maintenance Therapy (Feasibility Analysis Population)	Dose Level 2 (175 mg/m2)	40		% of participants
Percentage of Participants Observed to Have Unacceptable Toxicity During the Intra-patient Dose Escalation of Temozolomide During Maintenance Therapy (Feasibility Analysis Population)	Dose Level 3 (200 mg/m2)	67		% of participants
Overall Survival	Phase II Patients + Phase I MTD Patients	5.3	95% Confidence Interval 0.0 to 12.4	Percent probability
Number of Phase I Patients Who Experienced Dose Limiting Toxicities (DLTs)	Phase I, Dose Level 1 (50 mg)	1		Participants
Number of Phase I Patients Who Experienced Dose Limiting Toxicities (DLTs)	Phase I, Dose Level 2 (65 mg)	0		Participants
Number of Phase I Patients Who Experienced Dose Limiting Toxicities (DLTs)	Phase I, Dose Level 3 (85 mg)	3		Participants
Progression-free Survival (PFS)	Phase II Patients + Phase I MTD Patients	2.9	95% Confidence Interval 0.0 to 6.8	Percent probability
Percentage of Patients With Pseudo Progression	Phase I, Dose Level 1 (50 mg)	33.3	95% Confidence Interval 6.3 to 72.9	Percentage of participants

1 to 10 of 109Source ClinicalTrials.gov

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Participant flow48

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
PHASE I: Veliparib + Radiation Therapy	STARTED	Phase I, Dose Level 1 (50 mg)	6
PHASE I: Veliparib + Radiation Therapy	STARTED	Phase I, Dose Level 2 (65 mg)	6
PHASE I: Veliparib + Radiation Therapy	STARTED	Phase I, Dose Level 3 (85 mg)	6
PHASE I: Veliparib + Radiation Therapy	STARTED	Phase II (MTD)	0
PHASE I: Veliparib + Radiation Therapy	COMPLETED	Phase I, Dose Level 1 (50 mg)	5
PHASE I: Veliparib + Radiation Therapy	COMPLETED	Phase I, Dose Level 2 (65 mg)	6
PHASE I: Veliparib + Radiation Therapy	COMPLETED	Phase I, Dose Level 3 (85 mg)	6
PHASE I: Veliparib + Radiation Therapy	COMPLETED	Phase II (MTD)	0
PHASE I: Veliparib + Radiation Therapy	NOT COMPLETED	Phase I, Dose Level 1 (50 mg)	1
PHASE I: Veliparib + Radiation Therapy	NOT COMPLETED	Phase I, Dose Level 2 (65 mg)	0

1 to 10 of 48Source ClinicalTrials.gov

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Adverse events596

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Anemia	Blood and lymphatic system disorders	Phase I, Dose Level 1 (50 mg/m2)	4	6	11
other	Anemia	Blood and lymphatic system disorders	Phase I, Dose Level 2 (65 mg/m2)	4	6	20
other	Anemia	Blood and lymphatic system disorders	Phase I, Dose Level 3 (85 mg/m2)	6	6	13
other	Anemia	Blood and lymphatic system disorders	Phase II (MTD)	27	47	59
other	Febrile neutropenia	Blood and lymphatic system disorders	Phase I, Dose Level 1 (50 mg/m2)	0	6	0
other	Febrile neutropenia	Blood and lymphatic system disorders	Phase I, Dose Level 2 (65 mg/m2)	0	6	0
other	Febrile neutropenia	Blood and lymphatic system disorders	Phase I, Dose Level 3 (85 mg/m2)	1	6	1
other	Febrile neutropenia	Blood and lymphatic system disorders	Phase II (MTD)	0	47	0
other	Palpitations	Cardiac disorders	Phase I, Dose Level 1 (50 mg/m2)	1	6	1
other	Palpitations	Cardiac disorders	Phase I, Dose Level 2 (65 mg/m2)	0	6	0

1 to 10 of 596Source ClinicalTrials.gov

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Adverse event totals12

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Phase I, Dose Level 1 (50 mg/m2)	6	6
Total, all-cause mortality	Phase I, Dose Level 2 (65 mg/m2)	5	6
Total, all-cause mortality	Phase I, Dose Level 3 (85 mg/m2)	6	6
Total, all-cause mortality	Phase II (MTD)	40	47
Total, other adverse events	Phase I, Dose Level 1 (50 mg/m2)	6	6
Total, other adverse events	Phase I, Dose Level 2 (65 mg/m2)	6	6
Total, other adverse events	Phase I, Dose Level 3 (85 mg/m2)	6	6
Total, other adverse events	Phase II (MTD)	46	47
Total, serious adverse events	Phase I, Dose Level 1 (50 mg/m2)	5	6
Total, serious adverse events	Phase I, Dose Level 2 (65 mg/m2)	2	6

1 to 10 of 12Source ClinicalTrials.gov

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Papers2

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
32009149	DERIVED	PubMed
33571520	DERIVED	PubMed

Grants2

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

Project	Title	Principal investigators	Organization	Funder	Fiscal years	Source
UM1CA081457	Pediatric Brain Tumor Consortium A multi-institutional consortium devoted to novel phase I and II clinical evaluations of experimental treatment approaches for pediatric CNS tumors	ONAR-THOMAS, ARZU; DUNKEL, IRA J	ST. JUDE CHILDREN'S RESEARCH HOSPITAL	NATIONAL CANCER INSTITUTE	2014 to 2025	NIH RePORTER
U01CA081457	Pediatric Brain Tumor Consortium (PBTC)	BOYETT, JAMES MILFORD	ST. JUDE CHILDREN'S RESEARCH HOSPITAL	NATIONAL CANCER INSTITUTE	1999 to 2013	NIH RePORTER

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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Read this trial from software.

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