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Eligibility
for people ages 18 years and up
Location
at San Francisco, California and other locations
Dates
study started

Description

Summary

This randomized phase II/III trial studies how well temozolomide and veliparib work compared to temozolomide alone in treating patients with newly diagnosed glioblastoma multiforme. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether temozolomide is more effective with or without veliparib in treating glioblastoma multiforme.

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

Details

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 O-6-methylguanine-deoxyribonucleic acid (DNA) 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.

Keywords

Glioblastoma Gliosarcoma Temozolomide Dacarbazine Veliparib

Eligibility

For people ages 18 years and up

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
  • Platelets>= 100,000 cells/mm^3
  • Creatinine =< 1.5 x upper limit of normal (ULN)
  • Bilirubin =< 1.5 x ULN; unless patient has Gilbert's disease
  • Alanine aminotransferase (ALT) =< 3 x ULN
  • Aspartate aminotransferase (AST) =< 3 x ULN
  • 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
  • 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
  • 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
  • Comorbid conditions: patients are unable to participate due to the following:
  • Seizure disorder that is uncontrolled at the time of registration; the definition of controlled seizures is patients must be without seizures for at least 10 days prior to registration
  • 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

Locations

  • Kaiser Permanente-Deer Valley Medical Center
    Antioch, California, 94531, USA
  • Mills - Peninsula Hospitals
    Burlingame, California, 94010, USA
  • John Muir Medical Center-Concord Campus
    Concord, California, 94520, USA
  • Kaiser Permanente-Fremont
    Fremont, California, 94538, USA
  • Kaiser Permanente-Modesto
    Modesto, California, 95356, USA
  • Kaiser Permanente Oakland-Broadway
    Oakland, California, 94611, USA
  • Kaiser Permanente-Oakland
    Oakland, California, 94611, USA
  • Kaiser Permanente-Rancho Cordova Cancer Center
    Rancho Cordova, California, 95670, USA
  • Kaiser Permanente-Redwood City
    Redwood City, California, 94063, USA
  • Kaiser Permanente-Richmond
    Richmond, California, 94801, USA
  • Rohnert Park Cancer Center
    Rohnert Park, California, 94928, USA
  • Kaiser Permanente-Roseville
    Roseville, California, 95661, USA
  • The Permanente Medical Group-Roseville Radiation Oncology
    Roseville, California, 95678, USA
  • Sutter General Hospital
    Sacramento, California, 95816, USA
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, 95817, USA
  • Kaiser Permanente-South Sacramento
    Sacramento, California, 95823, USA
  • South Sacramento Cancer Center
    Sacramento, California, 95823, USA
  • Kaiser Permanente - Sacramento
    Sacramento, California, 95825, USA
  • Kaiser Permanente-San Francisco
    San Francisco, California, 94115, USA
  • Kaiser Permanente-Santa Teresa-San Jose
    San Jose, California, 95119, USA
  • Kaiser Permanente San Leandro
    San Leandro, California, 94577, USA
  • Kaiser Permanente-San Rafael
    San Rafael, California, 94903, USA
  • Kaiser Permanente Medical Center - Santa Clara
    Santa Clara, California, 95051, USA
  • Palo Alto Medical Foundation-Santa Cruz
    Santa Cruz, California, 95065, USA
  • Kaiser Permanente-Santa Rosa
    Santa Rosa, California, 95403, USA
  • Kaiser Permanente Cancer Treatment Center
    South San Francisco, California, 94080, USA
  • Kaiser Permanente-South San Francisco
    South San Francisco, California, 94080, USA
  • Kaiser Permanente-Stockton
    Stockton, California, 95210, USA
  • Northbay Cancer Center
    Vacaville, California, 95687, USA
  • Kaiser Permanente Medical Center-Vacaville
    Vacaville, California, 95688, USA
  • Kaiser Permanente-Vallejo
    Vallejo, California, 94589, USA
  • Kaiser Permanente-Walnut Creek
    Walnut Creek, California, 94596, USA
  • John Muir Medical Center-Walnut Creek
    Walnut Creek, California, 94598, USA
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California, 91505, USA
  • Fresno Cancer Center
    Fresno, California, 93720, USA
  • Kaiser Permanente
    Fresno, California, 93720, USA
  • Saint Jude Medical Center
    Fullerton, California, 92835, USA
  • UC San Diego Moores Cancer Center
    La Jolla, California, 92093, USA
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California, 90027, USA
  • Los Angeles County-USC Medical Center
    Los Angeles, California, 90033, USA
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California, 90033, USA
  • USC Norris Oncology/Hematology-Newport Beach
    Newport Beach, California, 92663, USA
  • Saint Joseph Hospital - Orange
    Orange, California, 92868, USA
  • University of California San Diego
    San Diego, California, 92103, USA

Details

Status
currently not accepting new patients, but might later
Start Date
Sponsor
National Cancer Institute (NCI)
ID
NCT02152982
Phase
Phase 2/3
Study Type
Interventional
Last Updated
November 2016