Temozolomide With or Without Veliparib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
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| ClinicalTrials.gov Identifier: NCT02152982 |
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Recruitment Status :
Active, not recruiting
First Posted : June 2, 2014
Last Update Posted : November 6, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Glioblastoma Gliosarcoma | Other: Laboratory Biomarker Analysis Other: Placebo Other: Quality-of-Life Assessment Drug: Temozolomide Drug: Veliparib | Phase 2 Phase 3 |
PRIMARY OBJECTIVES:
I. Test whether the experimental combination of ABT-888 (veliparib) combined with TMZ (temozolomide), compared to the control of placebo combined with TMZ, significantly extends overall survival in newly diagnosed glioblastoma multiforme (GBM) patients with tumor MGMT promoter hypermethylation.
SECONDARY OBJECTIVES:
I. Test whether the experimental treatment significantly extends progression-free survival.
II. Test whether the experimental treatment improves objective tumor response. III. Test whether the experimental treatment is associated with significantly greater rates of grade 3 or higher adverse events.
TERTIARY OBJECTIVES:
I. Evaluate the utility of dynamic susceptibility contrast (DSC) and diffusion weighted imaging (DWI) magnetic resonance imaging (MRI) techniques in defining time to progression in the setting of a large multi-institutional clinical trial.
II. Test the concordance between site-determined MGMT methylation status and central laboratory determination of MGMT status in cases with local testing.
III. Evaluate whether genetic or epigenetic alterations in deoxyribonucleic acid (DNA) repair or replication genes are associated with overall survival, progression-free survival, and objective tumor response.
IV. Test whether polymorphisms in MGMT, PARP1, or other DNA repair proteins, are associated with overall survival, progression-free survival, objective tumor response, or rates of grade 3 or higher adverse events.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5 and veliparib PO twice daily (BID) on days 1-7. Treatment repeats every 28 days for 6 courses in the absence of disease progression (confirmed progression) or unacceptable toxicity.
ARM II: Patients receive temozolomide as in Arm I and placebo PO BID on days 1-7. Treatment repeats every 28 days for 6 courses in the absence of disease progression (confirmed progression) or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 3 years, every 6 months for 2 years.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 440 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase II/III Randomized Trial of Veliparib or Placebo in Combination With Adjuvant Temozolomide in Newly Diagnosed Glioblastoma With MGMT Promoter Hypermethylation |
| Actual Study Start Date : | December 15, 2014 |
| Estimated Primary Completion Date : | January 14, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (temozolomide, veliparib)
Patients receive temozolomide PO QD on days 1-5 and veliparib PO BID on days 1-7. Treatment repeats every 28 days for 6 courses in the absence of disease progression (confirmed progression) or unacceptable toxicity.
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Other: Laboratory Biomarker Analysis
Correlative studies Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Drug: Temozolomide Given PO
Other Names:
Drug: Veliparib Given PO
Other Names:
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Placebo Comparator: Arm II (temozolomide, placebo)
Patients receive temozolomide as in Arm I and placebo PO BID on days 1-7. Treatment repeats every 28 days for 6 courses in the absence of disease progression (confirmed progression) or unacceptable toxicity.
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Other: Laboratory Biomarker Analysis
Correlative studies Other: Placebo Given PO
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Drug: Temozolomide Given PO
Other Names:
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- Overall survival (OS) [ Time Frame: From study registration to the date of death due to any cause, assessed up to 10 years ]The distribution of OS for each arm will be estimated using the Kaplan-Meier method and compared with a stratified logrank test. Stratified Cox proportional hazard models will be used to estimate the hazard ratio for the treatment effect.
- Interaction with Optune device [ Time Frame: Up to 5 years ]Cox proportional hazards model will be used to evaluate whether there is a potential interaction between the treatment arm and the Optune device. If an interaction is detected, separate analyses of treatment effect (using Cox models) will be done for patients treated with the Optune device and patients who were not treated with the Optune device.
- Progression-free survival (PFS) [ Time Frame: From study registration to the date of first observation of disease progression or death due to any cause (whichever comes first), assessed up to 10 years ]The distribution of PFS for each arm will be estimated using the Kaplan-Meier method, and be compared using Cox proportional hazard models with all stratification factors adjusted.
- Objective tumor response, defined as complete response or partial response as specified in the Revised Assessment in Neuro-Oncology criteria [ Time Frame: Up to 5 years ]An objective tumor response will be evaluated for each patient and the tumor response rate will be summarized for each arm and compared using the Chi-square test.
- Overall adverse event rates for grade 3 or higher adverse events assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5 beginning April 1, 2018) [ Time Frame: Up to 5 years ]The overall adverse event rates for grade 3 or higher adverse events will be summarized and be compared using Chi-Square or Fisher's Exact tests between treatment arms. The maximum grade for each type of treatment-related adverse event will be recorded for each patient, and frequency tables for each arm will be reviewed to determine patterns. Treatment-related adverse events will be tabulated for each arm.
- Change in quality of life (QOL), measured by the fatigue/uniscale tool [ Time Frame: Baseline to up to 5 years ]The fatigue/uniscale tool will be used as a measure of QOL. Potential differences in fatigue levels of patients treated on the two different arms will be evaluated. Changes in this measure will be evaluated over the course of treatment for both arms and will be compared using a two-sample t-test at each timepoint. Will also compute a normalized area under the curve (AUC) for the values of each patient over time and compare the mean AUCs for patients on the two arms.
- MGMT status [ Time Frame: Baseline ]The concordance between site-determined MGMT methylation status and central laboratory determination of MGMT status will be analyzed using the Chi-Square test of proportions and 95% confidence intervals for the proportion of tests in disagreement with the local site.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologic documentation: newly diagnosed World Health Organization (WHO) grade IV intracranial glioblastoma or gliosarcoma; GBM with oligodendroglial features are NOT PERMITTED in this study if they are 1p19q codeleted; sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q codeletion status
- Sufficient tissue available for central pathology review and MGMT methylation status evaluation
- Patients who have had a local MGMT testing that is unmethylated are not allowed to participate
- Tumor MGMT promoter hypermethylation determined by central testing at MD Anderson
- Confirmation by central pathology review of WHO grade IV glioblastoma or gliosarcoma
- Absolute neutrophil count (ANC) >= 1500 cells/mm^3 (within 14 days prior to study registration)
- Platelets >= 100,000 cells/mm^3 (within 14 days prior to study registration)
- Creatinine =< 1.5 x upper limit of normal (ULN) (within 14 days prior to study registration)
- Bilirubin =< 1.5 x ULN (within 14 days prior to study registration; unless patient has Gilbert's disease)
- Alanine aminotransferase (ALT) =< 3 x ULN (within 14 days prior to study registration)
- Aspartate aminotransferase (AST) =< 3 x ULN (within 14 days prior to study registration)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Measurable disease or non-measurable disease; extent of resection: patients with complete resection, partial resection, or biopsy are eligible
- Progression: patients deemed to have progressive disease based on clinical deterioration after chemoradiation or radiographic progression outside of the radiation field are not eligible; patients deemed to have pseudoprogression are eligible
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Prior treatment:
- Must have completed standard radiotherapy and concomitant TMZ therapy as defined and determined by the study oncologist
- Besides concomitant TMZ with radiation, no other therapy (neo-adjuvant or adjuvant) can be given prior to study registration, including chemotherapy (also including Gliadel/carmustine [BCNU] wafers), biologics, immunotherapy, radiation therapy; the only exception is the Optune device (NovoTTF-100A), which may be started any time after end of radiation therapy up through the initiation of Cycle 1; intent to use Optune must be declared at registration for stratification
- No prior allogeneic bone marrow transplant or double umbilical cord blood transplantation
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Not pregnant and not nursing; females of childbearing potential must have negative urine or serum pregnancy test within 7 days of registration but before start of treatment; a female of childbearing potential is a sexually mature female who:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- Concomitant medications: patients receiving anticoagulation should be on stable dose 2 weeks prior to registration
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Comorbid conditions: patients are unable to participate due to the following:
- Generalized or partial seizure disorder that is uncontrolled at the time of registration; the definition of controlled generalized seizures is patients must be on a stable dose of anti-seizure medication and without generalized seizures for at least 10 days prior to registration; the definition of controlled partial seizures is patients must be on a stable dose of anti-seizure medication for at least 10 days prior to registration; patients with occasional breakthrough partial seizures are allowed at treating physician's discretion
- Grade 3 or 4 thromboembolic disease within 6 months (mo) of registration
- Known history of prolonged QT syndrome
- No history of major surgery =< 14 days prior to registration
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Patients must have adequate organ and marrow function measured within 28 days prior to administration of ABT-888 as defined below:
- >= 10.0 g/dL hemoglobin (Hb) with no blood transfusion in the past 28 days
- No Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS) or with features suggestive of AML/MDS
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02152982
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| Principal Investigator: | Jann N Sarkaria | Alliance for Clinical Trials in Oncology |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT02152982 History of Changes |
| Other Study ID Numbers: |
NCI-2014-00616 NCI-2014-00616 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) A071102 CALGB-A071102 A071102 ( Other Identifier: Alliance for Clinical Trials in Oncology ) A071102 ( Other Identifier: CTEP ) P50CA108961 ( U.S. NIH Grant/Contract ) U10CA180821 ( U.S. NIH Grant/Contract ) U10CA031946 ( U.S. NIH Grant/Contract ) |
| First Posted: | June 2, 2014 Key Record Dates |
| Last Update Posted: | November 6, 2019 |
| Last Verified: | May 2019 |
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Glioblastoma Gliosarcoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial |
Neoplasms, Nerve Tissue Temozolomide Veliparib Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors |