Phase 2 N=18 Treatment

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

Anaplastic Astrocytoma · Brain Stem Glioma · Childhood Mixed Glioma · Fibrillary Astrocytoma · Giant Cell Glioblastoma

Bottom Line

View on ClinicalTrials.gov: NCT01514201 ↗

Enrolled (actual)

Serious AEs

43.1%

Results posted

Aug 2019

Primary outcome: 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) — 65 mg/m2/dose BID

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: 3-Dimensional Conformal Radiation Therapy (Radiation); Intensity-Modulated Radiation Therapy (Radiation); Laboratory Biomarker Analysis (Other); Pharmacological Study (Other); Temozolomide (Drug); Veliparib (Drug)
Age: Pediatric, Adult
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Mar 2018

Outcome Measures

Outcome	Result	p-value
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)	65	—
PRIMARY Percentage of Participants Observed to Have Unacceptable Toxicity During the Intra-patient Dose Escalation of Temozolomide During Maintenance Therapy (Feasibility Analysis Population)	9; 40; 67	—
PRIMARY Overall Survival	5.3	—
PRIMARY Number of Phase I Patients Who Experienced Dose Limiting Toxicities (DLTs)	1; 0; 3	—
SECONDARY Progression-free Survival (PFS)	2.9	—
SECONDARY Percentage of Patients With Pseudo Progression	33.3; 16.7; 0; 12.8	—
SECONDARY Maximum Concentration of Veliparib (Cmax) on Days 1 and 4 (Measured in ng/mL) [Pharmacokinetic Parameter]	519; 843; 1074; 844; 409; 788	—
SECONDARY Mean Apparent Clearance (CL/F) for Veliparib [Pharmacokinetic Parameter]	16.1; 13.2; 15.8; 11.7	—
SECONDARY Maximum Concentration of Veliparib (Cmax) on Day 1 (Measured in μM) [Pharmacokinetic Parameter]	2.12; 3.45; 4.40; 3.45	—
SECONDARY Apparent Volume of Distribution (Vd/F) for Veliparib [Pharmacokinetic Parameter]	75.4; 56.1; 63.9; 73.1	—
SECONDARY Terminal Half-life (t1/2) for Veliparib [Pharmacokinetic Parameter]	5.18; 2.62; 4.45; 2.18	—
SECONDARY Trough for Veliparib [Pharmacokinetic Parameter]	58; 140; 163; 84	—

Summary

This phase I/II trial studies the side effects and the best dose of veliparib when given together with radiation therapy and temozolomide and to see how well they work in treating younger patients newly diagnosed with diffuse pontine gliomas. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing. Giving veliparib with radiation therapy and temozolomide may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

Patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined as tumors with a pontine epicenter and diffuse intrinsic involvement of the pons, are eligible without histologic confirmation; patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, anaplastic mixed glioma, or fibrillary astrocytoma
Patients with juvenile pilocytic astrocytoma, pilomyxoid astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible;
Patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician
Patient must be able to swallow oral medications to be eligible for study enrollment
Karnofsky >= 50% for patients > 16 years of age or Lansky >= 50% for patients = = 1,000/mm^3
Platelets >= 100,000/mm^3 (unsupported)
Hemoglobin >= 10 g/dL (unsupported)
Total bilirubin = = 2 g/dL
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
0.6 mg/dL (1 to = 16 years of age)
Female patients of childbearing potential must not be pregnant or breast-feeding; female patients of childbearing potential must have a negative serum or urine pregnancy test
Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study
Signed informed consent according to institutional guidelines must be obtained; assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria

Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results
Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
Patients with active seizures or a history of seizure are not eligible for study entry, with the exception of patients with documented febrile seizure

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01514201). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.