Bevacizumab and Irinotecan or Temozolomide in Treating Patients With Recurrent or Refractory Glioblastoma Multiforme or Gliosarcoma
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|ClinicalTrials.gov Identifier: NCT00433381|
Recruitment Status : Completed
First Posted : February 12, 2007
Results First Posted : May 1, 2013
Last Update Posted : May 23, 2014
|Condition or disease||Intervention/treatment||Phase|
|Adult Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Tumor||Drug: irinotecan hydrochloride Biological: bevacizumab Drug: temozolomide||Phase 2|
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.
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.
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, multicenter study. Patients are stratified according to age (< 50 vs >= 50 years of age) and Karnofsky performance status (70-80% vs 90-100%). Patients are randomized to 1 of 2 treatment arms with a 2:1 ratio (arm I:arm II).
ARM I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral temozolomide once daily on days 1-21.
ARM II: Patients receive bevacizumab IV as in Arm I followed by irinotecan hydrochloride IV over 90 minutes on days 1 and 15.
In both arms, treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. All patients undergo MRI at baseline and at every 2 courses (no 2-week MRI) per standard of care until progression or discontinuation of treatment to assess areas of breakdown of the blood-brain barrier. Patients undergo an additional MRI after study therapy. Consenting patients also undergo diffusion and perfusion MRI and magnetic resonance spectroscopic imaging for correlative studies.
After completion of study therapy, patients are followed up for at least 1 month.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||123 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase II Trial of Bevacizumab With Irinotecan or Bevacizumab With Temozolomide in Recurrent Glioblastoma|
|Study Start Date :||March 2007|
|Actual Primary Completion Date :||January 2010|
|Actual Study Completion Date :||February 2011|
Experimental: Arm I (bevacizumab and temozolomide)
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral temozolomide once daily on days 1-21.
Experimental: Arm II (bevacizumab and irinotecan hydrochloride)
Patients receive bevacizumab IV as in Arm I followed by irinotecan hydrochloride IV over 90 minutes on days 1 and 15.
Drug: irinotecan hydrochloride
- 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.
- 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. ]
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): NCT00433381
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|Principal Investigator:||Mark Gilbert||Radiation Therapy Oncology Group|