PBTC-033: A Phase I/ II Study of ABT-888, an Oral Poly (ADP-ribose) Polymerase Inhibitor, and Concurrent Radiation Therapy, Followed by ABT-888 and Temozolomide, in Children with Newly Diagnosed Diffuse Pontine Gliomas (DIPG).
What is the purpose of this study?
This phase I/II trial studies the side effects and the best dose of veliparib giving together with radiation therapy and temozolomide and to see how well it works in treating younger patients newly diagnosed with diffuse pontine gliomas.
Who can participate?
- Patient must be able to swallow oral medications to be eligible for study enrollment
- Karnofsky ≥ 50% for patients >16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age (patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score)
- Absolute neutrophil count ≥ 1,000/mm³
- Platelets ≥ 100,000/mm³ (unsupported)
- Hemoglobin ≥ 10 g/dL (unsupported)
- Creatinine clearance or radioisotope GFR ≥ 70 mL/min or a serum creatinine based on age/gender as follows:
- 0.6 mg/dL (1 to < 2 years of age)
- 0.8 mg/dL (2 to < 6 years of age)
- 1.0 mg/dL (6 to < 10 years of age)
- 1.2 mg/dL (10 to < 13 years of age)
- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
- 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
- Total bilirubin (sum of conjugated and unconjugated) ≤ 1.5 times upper limit of normal (ULN)
- Serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 5 times institutional ULN
- Albumin ≥ 2 g/dL
- 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
- No 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
- No patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
- Patients with uncontrolled seizures are not eligible for study entry
PRIOR CONCURRENT THERAPY:
- Patients must have not received any prior therapy other than surgery and/or steroids
- Other concurrent anticancer or experimental agents or therapies are not permitted
- Cancer - Brain and Spinal Tumors
What is involved?
This is a dose-escalation, phase I study of veliparib followed by a phase II study.
Dose-escalation: Patients receive veliparib orally (PO) twice daily (BID) 5 days a week for 6-7 weeks. Patients also undergo concurrent 3-dimensional conformal or intensity-modulated radiotherapy once daily (QD) 5 days a week for 6-7 weeks.
Maintenance therapy: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic studies (required in phase I, optional in phase II). Patients may also undergo peripheral blood mononuclear cells and urine sample collection for PARP activity, γ-H2AX levels, and other biomarker studies. Tumor tissue samples from biopsy may be also collected.
After completion of study treatment, patients are followed up periodically for up to 3 years.
Who should I contact for more information?
For more information contact:
Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Where can I find additional information?