Inclusion Criteria

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 ≥ 9.0 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

PRIOR CONCURRENT THERAPY:

- 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

- Patients in stage 1 of the study only may receive additional anticancer
therapies as soon as the resection has been performed