A Randomized Phase II Trial of Bevacizumab With Irinotecan or Bevacizumab With Temozolomide in Recurrent Glioblastoma
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
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 an overall 1:1 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.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Six-month Progression-free Survival (PFS) for Bevacizumab and Irinotecan Hydrochloride Arm
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.
From randomization to six months.
American College of Radiology Imaging Network
United States: Food and Drug Administration
|University of Iowa Hospitals and Clinics||Iowa City, Iowa 52242|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|University of Washington Medical Center||Seattle, Washington 98195-6043|
|Henry Ford Hospital||Detroit, Michigan 48202|
|LDS Hospital||Salt Lake City, Utah 84143|
|William Beaumont Hospital||Royal Oak, Michigan 48073|
|Carolinas Medical Center||Charlotte, North Carolina 28232-2861|
|Mobile Infirmary Medical Center||Mobile, Alabama 36640-0460|
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|
|Northern Rockies Radiation Oncology Center||Billings, Montana 59101|
|American Fork Hospital||American Fork, Utah 84003|
|Cottonwood Hospital Medical Center||Murray, Utah 84107|
|McKay-Dee Hospital Center||Ogden, Utah 84403|
|Sutter Solano Medical Center||Vallejo, California 94589|
|Grandview Hospital||Dayton, Ohio 45405|
|Miami Valley Hospital||Dayton, Ohio 45409|
|Adventist Medical Center||Portland, Oregon 97216|
|Greene Memorial Hospital||Xenia, Ohio 45385|
|University of Rochester||Rochester, New York 14642|
|Yale University||New Haven, Connecticut 06520|
|Dartmouth Hitchcock Medical Center||Lebanon, New Hampshire 03756|
|Virginia Mason CCOP||Seattle, Washington 98101|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|M D Anderson Cancer Center||Houston, Texas 77030|
|Froedtert and the Medical College of Wisconsin||Milwaukee, Wisconsin 53226|
|Saint Francis Hospital and Health Centers||Beech Grove, Indiana 46107|
|Reid Hospital and Health Care Services||Richmond, Indiana 47374|
|Cheshire Medical Center-Dartmouth-Hitchcock Keene||Keene, New Hampshire 03431|
|Highland Hospital||Rochester, New York 14620|
|Mission Hospitals Inc||Asheville, North Carolina 28801|
|Good Samaritan Hospital - Dayton||Dayton, Ohio 45406|
|Dayton CCOP||Dayton, Ohio 45429|
|Samaritan North Health Center||Dayton, Ohio 45415|
|Veteran Affairs Medical Center||Dayton, Ohio 45428|
|Blanchard Valley Hospital||Findlay, Ohio 45840|
|Atrium Medical Center-Middletown Regional Hospital||Franklin, Ohio 45005-1066|
|Kettering Medical Center||Kettering, Ohio 45429|
|Upper Valley Medical Center||Troy, Ohio 45373|
|Saint Francis Hospital||Federal Way, Washington 98003|
|Evergreen Hospital Medical Center||Kirkland, Washington 98033|
|John F Kennedy Medical Center||Edison, New Jersey 08818|
|Sandra L Maxwell Cancer Center||Cedar City, Utah 84720|
|Intermountain Medical Center||Murray, Utah 84157|
|Utah Valley Regional Medical Center||Provo, Utah 84603|
|Dixie Medical Center Regional Cancer Center||Saint George, Utah 84770|
|Intermountain Health Care||Salt Lake City, Utah 84103|
|Utah Cancer Specialists-Salt Lake City||Salt Lake City, Utah 84106|
|Fairbanks Memorial Hospital||Fairbanks, Alaska 99701|
|Boca Raton Regional Hospital||Boca Raton, Florida 33486|
|Norris Cotton Cancer Center-North||Saint Johnsbury, Vermont 05819|