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A RANDOMIZED PHASE VII STUDY OF ABT--888 IN COMBINATION WITH TEMOZOLOMIDE IN TEMOZOLOMIDE REISISTANT GLIOBLASTOMA (IRB #235086)
The purpose of this study is to test the safety and efficacy of the ABT-888 in patients with recurrent glioblastoma (GBM) or GBM's resistant to current SOC treatment which is surgery, chemotherapy (temozolomide) and radiation. Previous research shows that adding another drug to the SOC may help the tumor overcome its resistance to temozolomide and bring it under control. 240 patients will take part in the study, a total of 10 at CSMC.
Patients who present to the Department of Neurosurgery and Neurology at CSMC as well as subjects referred by outside neurologist who meet study criteria will be screened and consent obtained.
In order to determine eligibility the study doctor will perform the following test: History and Physical, MRI of the brain, blood test including blood counts, as well as liver and kidney function test, blood pregnancy screen and urinalysis. If a patient is eligible to participate these test will be repeated before entering phase l of the trial.
Patients entering phase l will receive temozolomide and ABT- 888 on days 1-21 of a 28-day schedule. Patients can receive this combination indefinitely unless their disease progresses or they develop unwarranted side effects. If a patient needs to stop the study treatment, other treatment options will be discussed. Medications will be taken orally on an empty stomach. The ABT-888 will be taken twice a day. One of the doses will be taken at bedtime with temozolomide. About 1 hour before taking your temozolomide and ABT-888 patients will also take an anti-nausea drug which the study doctor will prescribe.
Phase I: Dose Level Temozolomide Dose ABT-888 Dose:
- 1. 60 mg/m2 x 21 days, 20 mg BID x 21 days
- 2. a: 60 mg/m2 x 21 days, 40 mg BID x 21 days
- 2. b. 75 mg/m2 x 21 days, 20 mg BID x 21 days
- 3. 75 mg/m2 x 21 days, 40 mg BID x 21 days
Patients entering into phase II of the study, will be randomized to 1 of 2 groups:
- Group 1 will receive temozolomide and ABT-888 at the maximum safe dose level combination determined from phase I portion of the study. Patients will receive the temozolomide and ABT-888 on days 1-21 of a 28-day schedule, as was given in the phase I portion.
- Group 2 will receive temozolomide and ABT-888 at a dose level combination already determined to be safe in an earlier study. Patients will receive the temozolomide and ABT-888 on days 1-5 of a 28-day schedule.
Medications will be taken as was taken in phase l. Patients receiving the temozolomide and ABT-888 will visit the study doctor for regular office visits every 28 days, they will also receive blood tests to monitor how the study drugs are affecting their body. These tests will be performed monthly (and may be performed weekly if the patient experiences any toxicities such as an elevated ANC or platelet count). Patients will be asked to complete a medication diary to help document when medication is taken and any side effects experienced.
Patients will be asked to take the temozolomide and ABT-888 combination for as long as they are benefiting from it. If treatment needs to be stopped other treatment options will be discussed.
Most of the procedures in this study are considered to be standard of care and will be billed to the patient and/or their insurance. The collection of the optional tumor sample is considered to be research-related and will be covered by RTOG. Temozolomide will be billed to subjects/subjects' insurance.
This study also includes a specimen collection sub-study to collect a portion of the tumor tissue that is collected before subjects start treatment, in order to confirm their eligibility in this study. This tissue will be sent to the sponsor for storage in a repository for future research. Subjects will sign a separate consent for participation in this portion of the research.
Surasak Phuphanich, MD, FAAN
Director, Neuro-oncology Program