Veliparib and Temozolomide in Treating Patients With Recurrent Glioblastoma
- Conditions
- Brain and Central Nervous System Tumors
- Interventions
- Drug: ABT-888 20 mg x 21 daysDrug: ABT-888 40 mg x 21 daysDrug: ABT-888 40 mg x 5 days
- Registration Number
- NCT01026493
- Lead Sponsor
- Radiation Therapy Oncology Group
- Brief Summary
RATIONALE: Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide. work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving veliparib together with temozolomide may kill more tumor cells.
PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of giving veliparib together with temozolomide and to see how well it works in treating patients with recurrent glioblastoma.
- Detailed Description
OBJECTIVES:
Primary
* To define the maximum-tolerated dose of the combination of temozolomide and veliparib in patients with recurrent glioblastoma previously or not treated with temozolomide. (Phase I\*)
* To determine the efficacy of the combination of temozolomide and veliparib (using a 5-day vs 21-day schedule) as measured by the 6-month progression-free survival rate in patients with recurrent glioblastoma previously treated with temozolomide. (Phase II\*)
Secondary
* To characterize the safety profile of the combination of temozolomide and veliparib. (Phase I\*)
* To determine the adverse event profile and tolerability of the combination of temozolomide and veliparib (using a 5-day vs 21-day schedule) in patients with recurrent glioblastoma. (Phase II\*)
* To determine the efficacy of the combination of temozolomide and veliparib (using a 5-day vs 21-day schedule) as measured by objective response in patients with measurable disease. (Phase II\*)
* To determine the overall survival of patients treated with the combination of temozolomide and veliparib (using a 5-day vs 21-day schedule). (Phase II\*) Note: \*Phase I was closed and phase II was opened on 3/6/12.
OUTLINE: This is a multicenter, phase I\* dose-escalation study followed by a phase II\* randomized study. Patients enrolled in the phase II portion are stratified according to bevacizumab (BEV) status (bevacizumab-naive vs bevacizumab-failure), age (\< 50 years vs ≥ 50 years), Karnofsky performance status (70-80% vs 90-100%), and recent resection (yes vs no/biopsy only).
* Phase I:\* Patients receive oral temozolomide once daily and oral veliparib twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
* Phase II:\* Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive temozolomide and veliparib as in phase I.
* Arm II: Patients receive oral temozolomide once daily and oral veliparib twice daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks for 1 year, every 26 weeks for 2 years, and then annually thereafter.
Note: \*Phase I was closed and phase II was opened on 3/6/12.
PROJECTED ACCRUAL: A total of 240 patients (28 for phase I\* and 212 for phase II\*) will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 257
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase II: Arm 2/BEV-FAILURE Temozolomide 150 mg x 5 days ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days Phase I: Dose Level 1 temozolomide 60 mg x 21 days ABT-888 20 mg x 21 days plus temozolomide 60 mg x 21 days Phase I: Dose Level 1 ABT-888 20 mg x 21 days ABT-888 20 mg x 21 days plus temozolomide 60 mg x 21 days Phase I: Dose Level 2a temozolomide 60 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 60 mg x 21 days Phase I: Dose Level 2a ABT-888 40 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 60 mg x 21 days Phase II: Arm 2/BEV-FAILURE ABT-888 40 mg x 5 days ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days Phase I: Dose Level 2b ABT-888 20 mg x 21 days ABT-888 20 mg x 21 days plus temozolomide 75 mg x 21 days Phase I: Dose Level 3 temozolomide 75 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days Phase I: Dose Level 3 ABT-888 40 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days Phase II: Arm 1/BEV-NAIVE temozolomide 75 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days Phase II: Arm 1/BEV-NAIVE ABT-888 40 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days Phase II: Arm 2/BEV-NAIVE Temozolomide 150 mg x 5 days ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days Phase II: Arm 2/BEV-NAIVE ABT-888 40 mg x 5 days ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days Phase II: Arm 1/BEV-FAILURE temozolomide 75 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days Phase I: Dose Level 2b temozolomide 75 mg x 21 days ABT-888 20 mg x 21 days plus temozolomide 75 mg x 21 days Phase II: Arm 1/BEV-FAILURE ABT-888 40 mg x 21 days ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days
- Primary Outcome Measures
Name Time Method Phase 1: Maximum Tolerated Dose (MTD) Start of treatment to 8 weeks. Dose limiting toxicity (DLT) = any of the following events within 1st 8 weeks of treatment attributable to study drugs: Any grade (gr) 3/4 thrombocytopenia, gr 4 anemia, gr 3 neutropenia with fever (\>100.4). gr 4 neutropenia lasting \> 7 days; Any non-hematologic (NH) gr 3+ toxicity (TOX), excluding alopecia, despite maximal medical therapy (MLT); NH TOX such as rash, nausea, vomiting, diarrhea, mucositis, hypophosphatemia, and hypertension will only be considered DLTs if they remain gr 3+ despite MLT; 2nd occurrence of thromboembolism; Failure to recover from TOX (\<= gr 1) to be eligible for re-treatment with study drugs \<= 14 days of last dose of either drug; Any episode of non-infectious radiologically observed pneumonitis gr 2-4 any duration. Dose level will be considered acceptable if \<= 1 of the 1st 6 eligible patients experiences a DLT. If current level is considered acceptable, dose escalation occurs. Otherwise preceding acceptable dose level will be declared the MTD.
Phase II: 6-month Progression-free Survival (PFS) Rate for Patients With Measurable Disease After Surgery Randomization to 6 months. For patients with measureable disease after surgery: Progression defined as ≥ 25% increase in size of enhancing tumor or any new tumor; or neurologically worse, and steroids stable/increased. Bevacizumab (BEV)-naïve group: p0= 15% as estimate of 6-mo. PFS \[null hypothesis (NH)\], p1= 30%, with a 15% absolute increase \[alternative hypothesis (AH)\]. Error rates of 10% alpha and 10% beta. If \<= 11 patients experience 6-month PFS of the first 53 analyzable patients, then do not reject the null hypothesis that the 6-month PFS rate of experimental arm is less than 15%; BEV-failure group: p0 = 2% as a conservative estimate of 6-month PFS \[NH\], p1 = 15%, with a 13% absolute increase \[AH\]. Using first 26 analyzable subjects for each experimental arm, there is \>= 90% power to detect \>= 15% increase at a significance level of 0.10, using a 1-sided binomial test. If \>= 2 patients (8%) are progression free at 6 mo., then claim this regimen to be promising in the patient group.
- Secondary Outcome Measures
Name Time Method Phase II: Objective Response (Partial and Complete Response) Rate for Patients With Measurable Disease After Surgery Analysis occurs after all patients have been on study for at 6 months. (Patients are followed from randomization to death or study termination whichever occurs first.) Response and progression will be evaluated using standard criteria for patients with malignant gliomas (Macdonald 1990). Partial response and complete response are centrally reviewed.
Phase II: Overall Survival (OS) Analysis occurs after all patients have been on study for at 6 months. (Patients are followed from randomization to death or study termination whichever occurs first.) Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur when all patients had been potentially followed for at least 6 months.
Trial Locations
- Locations (17)
Renown Institute for Cancer at Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Louisville Oncology at Norton Cancer Institute - Louisville
🇺🇸Louisville, Kentucky, United States
Regional Cancer Center at Singing River Hospital
🇺🇸Pascagoula, Mississippi, United States
Legacy Good Samaritan Hospital & Comprehensive Cancer Center
🇺🇸Portland, Oregon, United States
CCOP - Kansas City
🇺🇸Prairie Village, Kansas, United States
Leeward Radiation Oncology
🇺🇸'Ewa Beach, Hawaii, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Central Baptist Hospital
🇺🇸Lexington, Kentucky, United States
Rebecca and John Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
Queen's Cancer Institute at Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
Highland Hospital of Rochester
🇺🇸Rochester, New York, United States
Cancer Research Center of Hawaii
🇺🇸Honolulu, Hawaii, United States
Hawaii Medical Center - East
🇺🇸Honolulu, Hawaii, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States