Clinical Trial: Bevacizumab and Irinotecan or Temozolomide in Treating Patients With Recurrent or Refractory Glioblastoma Multiforme or Gliosarcoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized Phase II Trial of Bevacizumab With Irinotecan or Bevacizumab With Temozolomide in Recurrent Glioblastoma

Brief Summary: This randomized phase II trial is studying the side effects and how well giving bevacizumab together with irinotecan or temozolomide works in treating patients with recurrent or refractory glioblastoma multiforme or gliosarcoma. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with irinotecan or temozolomide may kill more tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the efficacy of bevacizumab and irinotecan hydrochloride, in terms of 6-month progression-free survival rate, in patients with recurrent or refractory intracranial glioblastoma multiforme or gliosarcoma.

II. Determine the adverse event profile and tolerability of bevacizumab and temozolomide in these patients.

SECONDARY OBJECTIVES:

I. Determine the efficacy of bevacizumab and temozolomide, in terms of 6-month progression-free survival rate, in patients previously treated with temozolomide.

II. Determine the efficacy of bevacizumab and irinotecan hydrochloride, in terms of objective response, in patients with measurable disease.

III. Determine the efficacy of bevacizumab and temozolomide, in terms of objective response, in patients with measurable disease who were previously treated with temozolomide.

IV. Determine the toxicity profile and tolerability of bevacizumab and irinotecan hydrochloride in these patients.

TERTIARY OBJECTIVES:

I. Assess the potential role of perfusion MRI and magnetic resonance spectroscopy imaging as an early indicator of response to therapy after 2 weeks of treatment with bevacizumab.

II. Assess the potential role of perfusion MRI and magnetic resonance spectroscopy imaging as a prognostic indicator based on images taken at baseline, at 2 weeks, and after 2 courses of study treatment.

OUTLINE: This is a randomized, multicen
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

• Six-month Progression-free Survival (PFS) for Bevacizumab and Irinotecan Hydrochloride Arm [ Time Frame: From randomization to six months. ]
  Progression-free survival is defined as time from randomization to date of progression or date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive without progression are considered to be censored at the date of last contact.
• Rate of Treatment Discontinuation Due to Treatment-related Medical Complications(Bevacizumab and Temozolomide Arm) [ Time Frame: From randomization to end of treatment (treatment can continue up to 24 months for patients with stable or responding tumor). ]
  If 6 or fewer of 29 patients stop treatment due to medical conditions, then null hypothesis of rate = 0.35 will be rejected, type I and type II error of 0.10. Alternative hypothesis rate of 0.15.

Original Primary Outcome:

• 6-month progression-free survival rate (bevacizumab and irinotecan hydrochloride arm)
• Rate of treatment-related adverse events (bevacizumab and temozolomide arm)

Current Secondary Outcome:

• Six-month Progression-free Survival (Bevacizumab and Temozolomide Arm) [ Time Frame: From randomization to six months. ]
• Best Objective Response Rate (Complete Response, Partial Response, Stable Disease, Progression) in Both Arms [ Time Frame: From randomization to progression, death, or last follow-up. ]
  Only patients who have measurable disease present at baseline will be considered evaluable for response except those who are removed from the study before the end of cycle 1 for reasons other than clinical progression (such as toxicity). Tumor size will be measured in millimeters and is the largest crosssectional area using perpendicular measurements of contrast enhancing abnormality. Complete response (CR): Complete disappearance of all enhancing tumor on consecutive MRI scans at least 1 month apart, off corticosteroids, and neurologically stable or improved. Partial response (PR): ≥ 50% decrease in size of enhancing tumor on consecutive MRI scans at least 1 month apart, corticosteroids stable or reduced, and neurologically stable or improved. Stable disease (SD): Does not qualify for CR, PR, or PD. Progression: ≥ 25% increase in the size of enhancing tumor or any new tumor; or neurologically worse, and steroids stable or increased.
• Agreement Between Local Interpretation and Central Interpretation of the Standard MRI on the 6-month Progression-free Survival [ Time Frame: From randomization to six months. ]
  Assessed using a McNemar's test. The sensitivity and specificity of the local interpretation of the 6-month progression-free survival will be estimated using the central review as the reference standard. In particular, for patients progressed at 6 months according to central review, the sensitivity of the local interpretation will be estimated and the exact confidence interval will be calculated. The specificity and the associated exact confidence interval of the local interpretation will be calculated in a similar way.
• Accuracy of Local Interpretation on the 6-month Progression-free Survival Using Central Review as the Reference Standard [ Time Frame: From randomization to six months. ]
• Correlation of Degree of Cerebral Blood Volume (CBV) and Lactate (Lac) to N-acetylaspartate (NAA) (Lac/NAA) Ratio [ Time Frame: From registration to two weeks following initiation of bevacizumab. ]
• Correlation of Degree of Cerebral Blood Volume (CBV) and Lactate (Lac) to Patient Response [ Time Frame: From randomization to two weeks following initiation of bevacizumab. ]
• Predictive Value of CBV and Lac/NAA in Assessing 6-month Progression-free Survival [ Time Frame: From randomization to six months. ]

Original Secondary Outcome:

• 6-month progression-free survival rate (bevacizumab and temozolomide arm)
• Objective response rate (complete response, partial response, stable disease, disease progression) at baseline, at 2 weeks, and after 2 courses of study treatment in patients with measurable disease
• Rate of treatment-related adverse events as measured by NCI CTCAE v3.0 (bevacizumab and irinotecan hydrochloride arm)
• Correlation of the degree of cerebral blood volume (CBV) and lactate (Lac) to N-acetylaspartate (NAA) (Lac/NAA) ratio with patient response at baseline and after 2 weeks of treatment with bevacizumab
• Predictive value of CBV and Lac/NAA in assessing 6-month progression-free survival as measured at baseline, at 2 weeks, and after 2 courses of study treatment

Dates:
Date Received: February 8, 2007
Date Started: March 2007
Date Completion:
Last Updated: May 7, 2014
Last Verified: November 2012