Temozolomide With or Without Veliparib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
This Phase II/III trial studies how well temozolomide (TMZ) and veliparib work in combination, compared to TMZ alone, in treating patients with newly diagnosed glioblastoma.
Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. TMZ does so by interfering with the cell’s DNA, which eventually triggers death of the cancer cell.
Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. More specifically, it inhibits PARP proteins that are required for DNA repair, potentially making cancer cells more susceptible to DNA-damaging chemotherapy drugs. It is not yet known whether TMZ is more effective with or without veliparib in treating glioblastoma, which is what this clinical trial aims to address.
- Histologic documentation: newly diagnosed World Health Organization (WHO) grade IV intracranial glioblastoma or gliosarcoma; GBM with oligodendroglial features are NOT PERMITTED in this study if they are 1p19q codeleted; sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q codeletion status
- Sufficient tissue available for central pathology review and MGMT methylation status evaluation
- Patients who have had a local MGMT testing that is unmethylated are not allowed to participate
- Tumor MGMT promoter hypermethylation determined by central testing at MD Anderson
- Confirmation by central pathology review of WHO grade IV glioblastoma or gliosarcoma
- Absolute neutrophil count (ANC) >= 1500 cells/mm^3 within 14 days prior to study registration
- Platelets >= 100,000 cells/mm^3 within 14 days prior to study registration
- Creatinine =< 1.5 x upper limit of normal (ULN) within 14 days prior to study registration
- Bilirubin =< 1.5 x ULN within 14 days prior to study registration; unless patient has Gilbert's disease
- Alanine aminotransferase (ALT) =< 3 x ULN within 14 days prior to study registration
- Aspartate aminotransferase (AST) =< 3 x ULN within 14 days prior to study registration
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Measurable disease or non-measurable disease; extent of resection: patients with complete resection, partial resection, or biopsy are eligible
- Progression: patients deemed to have progressive disease based on clinical deterioration after chemoradiation or radiographic progression outside of the radiation field are not eligible; patients deemed to have pseudoprogression are eligible
- Prior treatment:
- Must have completed standard radiotherapy and concomitant TMZ therapy as defined and determined by the study oncologist
- Besides concomitant TMZ with radiation, no other therapy (neo-adjuvant or adjuvant) can be given prior to study registration, including chemotherapy (also including Gliadel/carmustine [BCNU] wafers), biologics, immunotherapy, radiation therapy; the only exception is the Optune device (NovoTTF-100A), which may be started any time after end of radiation therapy up through the initiation of Cycle 1; intent to use Optune must be declared at registration for stratification
- Not pregnant and not nursing; females of childbearing potential must have negative urine or serum pregnancy test within 7 days of registration but before start of treatment; a female of childbearing potential is a sexually mature female who:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- Concomitant medications: patients receiving anticoagulation should be on stable dose 2 weeks prior to registration
- Comorbid conditions: patients are unable to participate due to the following:
- Generalized or partial seizure disorder that is uncontrolled at the time of registration; the definition of controlled generalized seizures is patients must be on a stable dose of anti-seizure medication and without generalized seizures for at least 10 days prior to registration; the definition of controlled partial seizures is patients must be on a stable dose of anti-seizure medication for at least 10 days prior to registration; patients with occasional breakthrough partial seizures are allowed at treating physician's discretion
- Grade 3 or 4 thromboembolic disease within 6 months (mo) of registration
- Known history of prolonged QT syndrome
- No history of major surgery =< 14 days prior to registration
For the most up-to-date list of criteria, please visit clinicaltrials.gov.