Details

Details

Title A Phase II/III randomized trial of Veliparib or placebo in combination with adjuvant Temozolomide in newly diagnosed Glioblastoma with MGMT promoter Hypermethylation

IRB A071102

CC 16-248

Hospital Main Campus

Phase Phase 2, Phase 3

Disease Glioblastoma

Drug Temozolomide, Veliparib

Description

Description

Primary objective
  • Test whether the experimental combination of ABT-888 (veliparib) combined with TMZ, compared to the control of placebo combined with TMZ, significantly extends overall survival in newly diagnosed GBM patients with tumor MGMT promoter hypermethylation.
Secondary objectives
  • Test whether the experimental treatment significantly extends progression-free survival.
  • Test whether the experimental treatment improves objective tumor response.
  • Test whether the experimental treatment is associated with significantly greater rates of grade 3 or higher adverse events.
Correlative Science Objectives
  • Evaluate the utility of dynamic susceptibility contrast (DSC) and diffusion weighted imaging (DWI) MRI techniques in defining time to progression in the setting of a large multi-institutional clinical trial.
  • Test the concordance between site-determined MGMT methylation status and central laboratory determination of MGMT status in cases with local testing.
  • Evaluate whether genetic or epigenetic alterations in DNA repair or replication genes are associated with overall survival, progression-free survival, and objective tumor response.
  • 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.
Inclusion Criteria

Inclusion Criteria

Pre-Registration Eligibility Criteria
  1. Histologic documentation: Newly diagnosed 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.
  2. Sufficient tissue available for central pathology review and MGMT methylation status evaluation.
  3. Age ≥ 18 years of age
  4. Patients who have had a local MGMT testing that is unmethylated are not allowed to participate.
Registration Eligibility Criteria
  1. Tumor MGMT promoter hypermethylation determined by central testing at MD Anderson.
  2. Confirmation by central pathology review of WHO Grade IV glioblastoma or gliosarcoma.
  3. Required Lab Values:
    • Required Initial Laboratory Values: (Within 14 days prior to study registration)
    • Absolute neutrophil count (ANC) ≥ 1500 cells/mm3
    • Platelets ≥ 100,000 cells/mm3
    • Creatinine ≤ 1.5x ULN
    • Bilirubin ≤ 1.5x ULN (Unless patient has Gilbert's disease)
    • ALT ≤ 3 x ULN
    • AST ≤ 3 x ULN
  4. ECOG Performance Status ≤ 2
  5. Measurable disease or non-measurable disease as defined in Section 11.0.
  6. Extent of resection: Patients with complete resection, partial resection, or biopsy are eligible.
  7. Progression: Patients deemed to have progressive disease based on clinical deterioration after chemoradiation or radiographic progression outside of the radiation field are not eligible. (See Section 11.4.3.2 for definition of clinical deterioration). Patients deemed to have pseudoprogression (as defined in Section 11.4.3.2) are eligible.
  8. Prior Treatment
    • Must have completed standard radiotherapy and concomitant TMZ therapy as defined in Appendix I 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, biologics, immunotherapy, radiation therapy, or Novo-TTF-100A System.
  9. Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. 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: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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).
  10. Concomitant Medications:
    • Patients receiving anticoagulation should be on stable dose 2 weeks prior to registration.
  11. 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 6mo of registration
    • Known history of prolonged QT syndrome
  12. No history of major surgery ≤ 14 days prior to registration
Exclusion Criteria

Exclusion Criteria

Exclusion Criteria Not Available