Bevacizumab and Irinotecan or Temozolomide in Treating Patients With Recurrent or Refractory Glioblastoma Multiforme or Gliosarcoma
Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Neoplasm
About this trial
This is an interventional treatment trial for Adult Glioblastoma
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed intracranial glioblastoma multiforme (GBM) or gliosarcoma
- Original histology of low-grade glioma with subsequent histological diagnosis of GBM or gliosarcoma allowed
Recurrent or refractory disease, meeting all of the following criteria:
- Must have received prior temozolomide
Pathologic or imaging confirmation of tumor progression or regrowth required
- Confirmation of true progressive disease (rather than radiation necrosis) by positron emission tomography, thallium scanning, MRI spectroscopy, or surgical documentation required for patients who received prior interstitial brachytherapy, Gliadel wafer, or stereotactic radiosurgery
- Unequivocal radiographic evidence of tumor progression by MRI within the past 14 days (while on a stable dose of steroids for ? 5 days)
No acute intratumoral hemorrhage on MRI
- Patients with MRI demonstrating old hemorrhage or subacute blood after a neurosurgical procedure (biopsy or resection) are eligible
- Karnofsky performance status 70-100%
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 6 months after completion of bevacizumab therapy
- Systolic blood pressure ? 160 mm Hg or diastolic blood pressure ? 90 mm Hg (antihypertensive medication allowed)
- Able to undergo brain MRI scans with intravenous gadolinium
- Absolute neutrophil count ? 1,500 cells/mm?
- Platelet count ? 100,000 cells/mm?
- Hemoglobin ? 10 g/dL (transfusion or other intervention allowed)
- WBC ? 3,000 cells/mm?
- AST < 2 times upper limit of normal
- Bilirubin ? 1.6 mg/dL
- Creatinine < 1.5 mg/dL
- Urine protein:creatinine ratio ? 0.5 by urinalysis OR total urinary protein < 1,000 mg by 24-hour urine collection
- INR < 1.4 (for patients not on warfarin)
- No patients with severely impaired renal function (i.e., estimated glomerular filtration rate < 30 mL/min or on dialysis)
- No other prior invasive malignancy, except nonmelanomatous skin cancer or carcinoma in situ of the cervix, unless the patient has been disease free and off therapy for that disease for ? 3 years
No severe, active comorbidity, defined as any of the following:
- Transmural myocardial infarction or unstable angina within the past 6 months
- Evidence of recent myocardial infarction or ischemia manifested as ST elevation of ? 2 mm by EKG performed within the past 14 days
- New York Heart Association class II-IV congestive heart failure requiring hospitalization within the past 12 months
- History of stroke or transient ischemic attack within the past 6 months
- Cerebrovascular accident within the past 6 months
- Serious and inadequately controlled cardiac arrhythmia
- Significant vascular disease (e.g., aortic aneurysm or history of aortic dissection)
- Clinically significant peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Serious or nonhealing wound, ulcer, or bone fracture
- Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study entry
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within the past 14 days
- Acquired immune deficiency syndrome (AIDS)
- No significant traumatic injury within the past 28 days
- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- No condition that impairs the ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication; requirement for IV alimentation; prior surgical procedures affecting absorption; or active peptic ulcer disease)
- No disease that would obscure toxicity or dangerously alter drug metabolism
- No concurrent major surgical procedures
- Recovered from prior therapy
Recent resection of recurrent or progressive tumor allowed provided the following criteria are met:
- Failed prior radiotherapy that was completed ? 42 days ago
- Residual disease after resection of recurrent glioblastoma is not mandated
- More than 28 days since prior surgery or open biopsy
- More than 7 days since prior core or needle biopsy
- At least 28 days since prior investigational agents
- At least 14 days since prior vincristine
- At least 42 days since prior nitrosoureas
- At least 21 days since prior procarbazine
- At least 28 days since other prior cytotoxic therapy
- At least 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin [except radiosensitizers])
At least 14 days since prior enzyme-inducing antiepileptic drugs (EIAEDs)
- Concurrent non-hepatic EIAEDs allowed
- No other concurrent CYP3A4 inducers, such as rifampin or Hypericum perforatum (St. John's wort)
Concurrent full-dose anticoagulants (e.g., warfarin or low molecular weight heparin) allowed provided all of the following criteria are met:
- No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
- In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulants or on a stable dose of low molecular weight heparin
- No concurrent highly active antiretroviral therapy
- No concurrent prophylactic use of growth factors
Sites / Locations
- Mobile Infirmary Medical Center
- Fairbanks Memorial Hospital
- Arizona Oncology Services Foundation
- Alta Bates Summit Medical Center-Herrick Campus
- Mills-Peninsula Medical Center
- John Muir Medical Center-Concord Campus
- City of Hope Comprehensive Cancer Center
- Marin General Hospital
- Sutter Cancer Research Consortium
- California Pacific Medical Center-Pacific Campus
- Sutter Solano Medical Center/Cancer Center
- John Muir Medical Center-Walnut Creek
- Yale University
- Boca Raton Regional Hospital
- University of Florida Health Science Center - Gainesville
- Saint Luke's Mountain States Tumor Institute
- University of Chicago Comprehensive Cancer Center
- Saint Vincent Anderson Regional Hospital/Cancer Center
- Franciscan Saint Francis Health-Beech Grove
- IU Health Methodist Hospital
- Reid Health
- University of Iowa/Holden Comprehensive Cancer Center
- Anne Arundel Medical Center
- University of Michigan Comprehensive Cancer Center
- Henry Ford Hospital
- Borgess Medical Center
- Bronson Methodist Hospital
- West Michigan Cancer Center
- William Beaumont Hospital-Royal Oak
- Fairview Ridges Hospital
- Mercy Hospital
- Fairview-Southdale Hospital
- Unity Hospital
- Minnesota Oncology Hematology PA-Maplewood
- Abbott-Northwestern Hospital
- North Memorial Medical Health Center
- Park Nicollet Clinic - Saint Louis Park
- United Hospital
- Ridgeview Medical Center
- Minnesota Oncology Hematology PA-Woodbury
- Washington University School of Medicine
- Northern Rockies Radiation Oncology Center
- Cheshire Medical Center-Dartmouth-Hitchcock Keene
- Dartmouth Hitchcock Medical Center
- John F Kennedy Medical Center
- New Mexico Oncology Hematology Consultants
- Memorial Sloan-Kettering Cancer Center
- Highland Hospital
- University of Rochester
- Mission Hospital-Memorial Campus
- Carolinas Medical Center/Levine Cancer Institute
- Akron General Medical Center
- Grandview Hospital
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Samaritan North Health Center
- Dayton NCI Community Oncology Research Program
- Veteran Affairs Medical Center
- Blanchard Valley Hospital
- Atrium Medical Center-Middletown Regional Hospital
- Kettering Medical Center
- Upper Valley Medical Center
- Greene Memorial Hospital
- Legacy Mount Hood Medical Center
- Providence Milwaukie Hospital
- Legacy Good Samaritan Hospital and Medical Center
- Providence Portland Medical Center
- Adventist Medical Center
- Providence Saint Vincent Medical Center
- Legacy Emanuel Hospital and Health Center
- Legacy Meridian Park Hospital
- Radiation Therapy Oncology Group
- Thomas Jefferson University Hospital
- Rhode Island Hospital
- M D Anderson Cancer Center
- American Fork Hospital / Huntsman Intermountain Cancer Center
- Sandra L Maxwell Cancer Center
- Cottonwood Hospital Medical Center
- Intermountain Medical Center
- McKay-Dee Hospital Center
- Utah Valley Regional Medical Center
- Dixie Medical Center Regional Cancer Center
- Intermountain Health Care
- Utah Cancer Specialists-Salt Lake City
- LDS Hospital
- Norris Cotton Cancer Center-North
- Saint Francis Hospital
- EvergreenHealth Medical Center
- Virginia Mason Medical Center
- University of Washington Medical Center
- PeaceHealth Southwest Medical Center
- University of Wisconsin Hospital and Clinics
- Froedtert and the Medical College of Wisconsin
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm I (bevacizumab and temozolomide)
Arm II (bevacizumab & irinotecan hydrochloride)
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral temozolomide once daily on days 1-21.
Patients receive bevacizumab IV as in Arm I followed by irinotecan hydrochloride IV over 90 minutes on days 1 and 15.