Study of the Poly (ADP-ribose) Polymerase-1 (PARP-1) Inhibitor BSI-201 in Patients With Newly Diagnosed Malignant Glioma

Inclusion criteria

• Patients must be at least 18 years of age
• Patients must have a Karnofsky performance status > 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
• Patients must have the following hematologic, renal and liver function (i.e. Absolute neutrophil count > 1500/mm3, Platelets > 100,000/mm3, creatinine < 1.7 mg/dl, total bilirubin ≤ 1.5 mg/dl, transaminases < 4 times above the upper limits of the institutional normal
• Patients must be able to provide written informed consent
• Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative pregnancy test. The anti-proliferative activity of this experimental drug as well as the standard drug (temozolomide) may be harmful to the developing fetus or nursing infant
• Patients must have a Mini Mental Status Exam score of > 15
• Patients must have tumor tissue form completed and signed by a pathologist. See section 9.6 for details

Phase I Criteria (Phase I Patients ONLY)

• Patients must have histologically proven supratentorial malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or glioblastoma multiforme)
• Patients must have received at least 80% of planned temozolomide and radiation therapy with no grade 3 or grade 4 toxicity attributed to the temozolomide
• Patients must have received planned treatment with radiation therapy and concomitant temozolomide at least 28 days but no more than 49 days prior to starting treatment on this study
• Patients must have Gadolinium MRI or contrast CT scan within 28 days of starting treatment

Exclusion criteria

• Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
• Patients who are pregnant or breast-feeding. The anti-proliferative activity of this experimental drug and temozolomide may be harmful to the developing fetus or nursing infant
• Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents)
• Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Patients who have been free of disease (any prior malignancy) for greater than five years are eligible for this study
• Patients cannot be receiving cytochrome P450-inducing anticonvulsants (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) and must not have taken them for at least 10 days

Phase I Ineligibility Criteria (Phase I Patients ONLY)

• Patients who have had repeat craniotomy for tumor therapy after receiving RT and TMZ treatment
• Patients who received other chemotherapeutics or investigational agents in addition to their radiation therapy and concomitant temozolomide treatment. Patients who have received Gliadel wafers are eligible for this study