Olaparib and Temozolomide in Treating Patients With Relapsed Glioblastoma

DISEASE CHARACTERISTICS:

* Histologically confirmed grade IV glioblastoma
* Radiological diagnosis of recurrent or progressive disease according to Response Assessment in Neuro-Oncology Working Group (RANO) criteria, which is suitable for palliative resection
* Must have an adequate amount of tumor tissue available
* Previously received first-line treatment with radical radiotherapy, or chemoradiation followed by adjuvant chemotherapy

  * No prior chemotherapy for recurrent disease

PATIENT CHARACTERISTICS:

* WHO performance status 0-2
* Life expectancy \> 12 weeks
* Hemoglobin ≥ 10.0 g/dL
* Absolute neutrophil count ≥ 1.5 x 10\^9/L
* Platelet count ≥ 100 x 10\^9/L
* Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
* ALT or AST ≤ 2.5 times ULN
* Calculated creatinine clearance ≥ 50 mL/min OR isotope clearance measurement ≥ 50 mL/min (uncorrected)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use one (male) or two (female) highly effective forms of contraception 4 weeks prior to, during, and for 6 months after completion of study therapy
* Able to swallow and retain oral medications
* Not at high medical risk due to non-malignant systemic disease, including active uncontrolled infection
* No known hepatitis B, hepatitis C, or HIV seropositivity
* No concurrent congestive heart failure, prior history of NYHA class III-IV cardiac disease, prior history of cardiac ischemia, or prior history of cardiac arrhythmia within the past 12 months
* No grand mal seizures occurring ≥ 3 times per week over the past month
* No gastrointestinal disorders likely to interfere with absorption of the study medication
* No known hypersensitivity to any of the components of olaparib
* No known hypersensitivity to temozolomide (TMZ) or any of its components, or to dacarbazine (DTIC) (for patients enrolled in stage 2 study only)
* No known lactose intolerance (for patients enrolled in the stage 2 study only)
* No metal fragments in the eyes (shrapnel or bullet injuries are excluded on the basis of their unsuitability to undergo MRI scans)
* No other condition which, in the Investigator's opinion, would not make the patient a good candidate for the clinical trial

EXCLUSION CRITERIA:

* See Disease Characteristics
* No ongoing toxic manifestations from previous treatments except for alopecia or grade 1 toxicities which, in the opinion of the Investigator and the Drug Development Office (DDO), should not exclude the patient
* At least 12 weeks since prior radiotherapy, endocrine therapy, or immunotherapy
* At least 6 weeks since prior major surgery
* At least 4 weeks since prior chemotherapy
* At least 4 weeks since prior immunizations with live vaccines (or expected to receive vaccines during the trial and up to at least 6 months after receiving last study treatment), including BCG and yellow fever vaccines
* No prior PARP inhibitors, including olaparib
* No prior major thoracic or abdominal surgery from which the patient has not yet recovered
* No prior heart surgery
* No pacemakers
* No change to systemic steroids dose within 5 days prior to enrollment (i.e., must be on a stable dose at time of enrollment and remain on a stable dose throughout the treatment period)
* No herbal supplements and/or ingestion of foods known to modulate CYP3A4 enzyme activity from time entered on screening period until 28 days after the last dose of study medication
* No concurrent drugs known to be potent inducers of CYP3A4, including phenytoin, carbamazepine, phenobarbital, rifampicin, rifapentine, rifabutin, nevirapine, modafinil, or St. John wort (wash-out period for phenobarbital is 5 weeks, 3 weeks for all others)
* No concurrent drugs known to be potent inhibitors of CYP3A4, including ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin, or nelfinavir (wash-out period is 1 week)
* No concurrent or planned participation in another interventional clinical study

  * Participation in an observational study is acceptable
* No concurrent warfarin (patients requiring anticoagulation should be given subcutaneous low molecular weight heparin)
* No other concurrent anticancer therapy (including radiotherapy) or investigational drugs

  * No blood transfusions within 4 weeks prior to study start of features suggestive of myelodysplasia or AML