Veliparib and Temozolomide in Treating Patients With Recurrent Glioblastoma
NCT ID: NCT01026493
Last Updated: 2017-07-02
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
257 participants
INTERVENTIONAL
2010-07-31
2016-12-31
Brief Summary
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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.
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Phase I: Dose Level 1
ABT-888 20 mg x 21 days plus temozolomide 60 mg x 21 days
temozolomide 60 mg x 21 days
Temozolomide 60 mg/m2 x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy.
ABT-888 20 mg x 21 days
20 mg bid x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy.
Phase I: Dose Level 2a
ABT-888 40 mg x 21 days plus temozolomide 60 mg x 21 days
temozolomide 60 mg x 21 days
Temozolomide 60 mg/m2 x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy.
ABT-888 40 mg x 21 days
40 mg bid x 21 days/28-day cycle. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude further therapy
Phase I: Dose Level 2b
ABT-888 20 mg x 21 days plus temozolomide 75 mg x 21 days
temozolomide 75 mg x 21 days
Temozolomide 75 mg/m2 x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy.
ABT-888 20 mg x 21 days
20 mg bid x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy.
Phase I: Dose Level 3
ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days
temozolomide 75 mg x 21 days
Temozolomide 75 mg/m2 x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy.
ABT-888 40 mg x 21 days
40 mg bid x 21 days/28-day cycle. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude further therapy
Phase II: Arm 1/BEV-NAIVE
ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days
temozolomide 75 mg x 21 days
Temozolomide 75 mg/m2 x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy.
ABT-888 40 mg x 21 days
40 mg bid x 21 days/28-day cycle. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude further therapy
Phase II: Arm 2/BEV-NAIVE
ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days
Temozolomide 150 mg x 5 days
150 mg/m2 x 5 days (up to 200 mg/m2 after 2nd cycle)\*, with a 28-day cycle; dose reduction to 125 mg/m2 if necessary. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude
ABT-888 40 mg x 5 days
40 mg bid x 5 days/28-day cycle. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude
Phase II: Arm 1/BEV-FAILURE
ABT-888 40 mg x 21 days plus temozolomide 75 mg x 21 days
temozolomide 75 mg x 21 days
Temozolomide 75 mg/m2 x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy.
ABT-888 40 mg x 21 days
40 mg bid x 21 days/28-day cycle. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude further therapy
Phase II: Arm 2/BEV-FAILURE
ABT-888 40 mg x 5 days plus temozolomide 150 mg x 5 days
Temozolomide 150 mg x 5 days
150 mg/m2 x 5 days (up to 200 mg/m2 after 2nd cycle)\*, with a 28-day cycle; dose reduction to 125 mg/m2 if necessary. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude
ABT-888 40 mg x 5 days
40 mg bid x 5 days/28-day cycle. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude
Interventions
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temozolomide 60 mg x 21 days
Temozolomide 60 mg/m2 x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy.
temozolomide 75 mg x 21 days
Temozolomide 75 mg/m2 x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy.
ABT-888 20 mg x 21 days
20 mg bid x 21 days, with a 28-day cycle. Treatment will continue until progressive disease unless toxicity or the discretion of the treating physician precludes further therapy.
ABT-888 40 mg x 21 days
40 mg bid x 21 days/28-day cycle. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude further therapy
Temozolomide 150 mg x 5 days
150 mg/m2 x 5 days (up to 200 mg/m2 after 2nd cycle)\*, with a 28-day cycle; dose reduction to 125 mg/m2 if necessary. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude
ABT-888 40 mg x 5 days
40 mg bid x 5 days/28-day cycle. Treatment continues until progressive disease unless toxicity or the discretion of the treating physician preclude
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patients must have recovered from the effects of surgery
* Residual disease following resection of recurrent glioblastoma is not mandated for eligibility into the study; to best assess the extent of residual disease post-operatively, a post-operative MRI scan should be performed within 28 days prior to registration and within 96 hours post surgery (although 24 hours would be optimum)
* Prior radiation is required for the phase I\* arm
* Patients must have completed a course of radiation therapy and at least 2 consecutive adjuvant cycles of temozolomide (phase II\*)
* A stable or decreasing dose of steroids at least 5 days prior to scanning is not mandated for patients who had a recent resection
* No evidence of acute (i.e., new and active) intratumoral hemorrhage on MRI
* Patients with MRI demonstrating old hemorrhage or subacute blood after a neurosurgical procedure (biopsy or resection) are eligible Note: \*Phase I was closed and phase II was opened on 3/6/12.
PATIENT CHARACTERISTICS:
* Karnofsky performance status 70-100%
* White blood cell (WBC) count ≥ 3,000/mm\^3
* Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
* Serum glutamic oxaloacetic transaminase (SGOT) ≤ 3.0 times upper limit of normal (ULN)
* Serum glutamic pyruvic transaminase (SGPT) ≤ 3.0 times ULN
* Bilirubin ≤ 1.25 times ULN
* Creatinine \< 1.7 mg/dL OR estimated glomerular filtration rate (GFR) ≥ 30 mL/min
* Urine protein:creatinine ratio ≤ 0.5 OR urine protein \< 1,000 mg by 24-hour urine collection\*\*
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
* Able to undergo brain MRI scans with IV gadolinium
* Able to swallow oral medications
* Patients with a history of seizure, or new onset of seizures, should be clinically controlled with no seizures for at least 14 days prior to registration
* No other prior invasive malignancy (except for nonmelanomatous skin cancer or carcinoma in situ of the cervix) unless the patient has been disease-free and off therapy for that disease for ≥ 3 years
* No severe, active comorbidity, including any of the following:
* Transmural myocardial infarction or unstable angina within the past 6 months
* Evidence of recent myocardial infarction or ischemia as indicated by S-T elevations of ≥ 2 mm on EKG performed within the past 14 days
* New York Heart Association (NYHA) class II-IV congestive heart failure requiring hospitalization within the past 12 months
* Stroke or transient ischemic attack within the past 6 months
* Cerebral vascular accident within the past 6 months
* Serious and inadequately controlled cardiac arrhythmia
* Clinically significant peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy
* Serious non-healing would, ulcer, or bone fracture
* Abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within the past 28 days
* Significant traumatic injury within the past 28 days
* Acute bacterial or fungal infection requiring IV antibiotics at the time of study registration
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within the past 14 days
* AIDS based upon current Centers for Disease Control and Prevention (CDC) definition (HIV testing is not required)
* No condition that would impair the ability to swallow pills (e.g., GI tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease)
* No disease that would obscure toxicity or dangerously alter drug metabolism
* Not on dialysis
* No history of chronic hepatitis B or C Note: \*\*Required for patients who received prior bevacizumab and developed known clinically significant nephrotic syndrome during treatment and whose baseline values have not returned to normal.
PRIOR CONCURRENT THERAPY:
* See Disease Characteristics
* Recovered from the toxic effects of prior therapy
* Prior interstitial brachytherapy, Gliadel wafer, or stereotactic radiosurgery allowed provided there is confirmation of progressive disease by positron emission tomography (PET) scan, thallium scan, MRI spectroscopy, perfusion MRI, or surgical documentation
* No more than 3 prior treatment regimens (phase I\*)
* No more than 2 prior treatment regimens for recurrent glioblastoma/gliosarcoma (phase II\*)
* More than 28 days since prior major surgical procedure or open biopsy (with the exception of craniotomy)
* At least 28 days since prior investigational agents or cytotoxic agents (42 days for nitrosoureas, 21 days for procarbazine, and 14 days for vincristine)
* At least 14 days since prior non-cytotoxic agents (e.g., bevacizumab, interferon, tamoxifen, thalidomide, isotretinoin, or tyrosine kinase inhibitors)
* No concurrent highly-active antiretroviral therapy
* No concurrent herbal products of unknown constitution
* No concurrent major surgical procedures Note: \*Phase I was closed and phase II was opened on 3/6/12.
18 Years
120 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
NRG Oncology
OTHER
Radiation Therapy Oncology Group
NETWORK
Responsible Party
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Principal Investigators
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H. Ian Robins, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Wisconsin, Madison
Mark R Gilbert, MD
Role: PRINCIPAL_INVESTIGATOR
National Cancer Institute/National Institutes of Health
Arnab Chakravarti, MD
Role: STUDY_CHAIR
Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Ohio State University Medical School
Locations
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Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States
Queen's Cancer Institute at Queen's Medical Center
Honolulu, Hawaii, United States
Hawaii Medical Center - East
Honolulu, Hawaii, United States
Leeward Radiation Oncology
‘Ewa Beach, Hawaii, United States
University of Chicago Cancer Research Center
Chicago, Illinois, United States
CCOP - Kansas City
Prairie Village, Kansas, United States
Central Baptist Hospital
Lexington, Kentucky, United States
Louisville Oncology at Norton Cancer Institute - Louisville
Louisville, Kentucky, United States
Regional Cancer Center at Singing River Hospital
Pascagoula, Mississippi, United States
Renown Institute for Cancer at Renown Regional Medical Center
Reno, Nevada, 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
Highland Hospital of Rochester
Rochester, New York, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States
Legacy Good Samaritan Hospital & Comprehensive Cancer Center
Portland, Oregon, United States
Countries
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Other Identifiers
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CDR0000660545
Identifier Type: -
Identifier Source: secondary_id
RTOG-0929
Identifier Type: -
Identifier Source: org_study_id
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