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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00433381
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

National Cancer Institute (NCI)
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Mark Gilbert
Principal Investigator Affiliation Radiation Therapy Oncology Group
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

NIH, Other
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Neoplasm
Additional Details

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, multicenter study. Patients are stratified according to age (< 50 vs.#46;>= 50 years of age) and Karnofsky performance status (70-80% vs.#46;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.

Arms & Interventions

Arms

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 & irinotecan hydrochloride)

Patients receive bevacizumab IV as in Arm I followed by irinotecan hydrochloride IV over 90 minutes on days 1 and 15.

Interventions

Biological: - Bevacizumab

Given IV

Drug: - Irinotecan Hydrochloride

Given IV

Drug: - Temozolomide

Given orally

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Mobile Infirmary Medical Center, Mobile, Alabama

Status

Address

Mobile Infirmary Medical Center

Mobile, Alabama, 36607

Fairbanks Memorial Hospital, Fairbanks, Alaska

Status

Address

Fairbanks Memorial Hospital

Fairbanks, Alaska, 99701

Arizona Oncology Services Foundation, Scottsdale, Arizona

Status

Address

Arizona Oncology Services Foundation

Scottsdale, Arizona, 85260

Berkeley, California

Status

Address

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, 94704

Mills-Peninsula Medical Center, Burlingame, California

Status

Address

Mills-Peninsula Medical Center

Burlingame, California, 94010

John Muir Medical Center-Concord Campus, Concord, California

Status

Address

John Muir Medical Center-Concord Campus

Concord, California, 94520

City of Hope Comprehensive Cancer Center, Duarte, California

Status

Address

City of Hope Comprehensive Cancer Center

Duarte, California, 91010

Marin General Hospital, Greenbrae, California

Status

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Marin General Hospital

Greenbrae, California, 94904

Sutter Cancer Research Consortium, Novato, California

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Sutter Cancer Research Consortium

Novato, California, 94945

San Francisco, California

Status

Address

California Pacific Medical Center-Pacific Campus

San Francisco, California, 94115

Vallejo, California

Status

Address

Sutter Solano Medical Center/Cancer Center

Vallejo, California, 94589

John Muir Medical Center-Walnut Creek, Walnut Creek, California

Status

Address

John Muir Medical Center-Walnut Creek

Walnut Creek, California, 94598

Yale University, New Haven, Connecticut

Status

Address

Yale University

New Haven, Connecticut, 06520

Boca Raton Regional Hospital, Boca Raton, Florida

Status

Address

Boca Raton Regional Hospital

Boca Raton, Florida, 33486

Gainesville, Florida

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Address

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610

Boise, Idaho

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Address

Saint Luke's Mountain States Tumor Institute

Boise, Idaho, 83712

Chicago, Illinois

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Address

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637

Anderson, Indiana

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Address

Saint Vincent Anderson Regional Hospital/Cancer Center

Anderson, Indiana, 46016

Beech Grove, Indiana

Status

Address

Franciscan Saint Francis Health-Beech Grove

Beech Grove, Indiana, 46107

IU Health Methodist Hospital, Indianapolis, Indiana

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Address

IU Health Methodist Hospital

Indianapolis, Indiana, 46202

Reid Health, Richmond, Indiana

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Address

Reid Health

Richmond, Indiana, 47374

Iowa City, Iowa

Status

Address

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242

Anne Arundel Medical Center, Annapolis, Maryland

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Address

Anne Arundel Medical Center

Annapolis, Maryland, 21401

Ann Arbor, Michigan

Status

Address

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109

Henry Ford Hospital, Detroit, Michigan

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Address

Henry Ford Hospital

Detroit, Michigan, 48202

Borgess Medical Center, Kalamazoo, Michigan

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Address

Borgess Medical Center

Kalamazoo, Michigan, 49001

Bronson Methodist Hospital, Kalamazoo, Michigan

Status

Address

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007

West Michigan Cancer Center, Kalamazoo, Michigan

Status

Address

West Michigan Cancer Center

Kalamazoo, Michigan, 49007

William Beaumont Hospital-Royal Oak, Royal Oak, Michigan

Status

Address

William Beaumont Hospital-Royal Oak

Royal Oak, Michigan, 48073

Fairview Ridges Hospital, Burnsville, Minnesota

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Address

Fairview Ridges Hospital

Burnsville, Minnesota, 55337

Mercy Hospital, Coon Rapids, Minnesota

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Address

Mercy Hospital

Coon Rapids, Minnesota, 55433

Fairview-Southdale Hospital, Edina, Minnesota

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Address

Fairview-Southdale Hospital

Edina, Minnesota, 55435

Unity Hospital, Fridley, Minnesota

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Address

Unity Hospital

Fridley, Minnesota, 55432

Maplewood, Minnesota

Status

Address

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, 55109

Abbott-Northwestern Hospital, Minneapolis, Minnesota

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Address

Abbott-Northwestern Hospital

Minneapolis, Minnesota, 55407

North Memorial Medical Health Center, Robbinsdale, Minnesota

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Address

North Memorial Medical Health Center

Robbinsdale, Minnesota, 55422

Park Nicollet Clinic - Saint Louis Park, Saint Louis Park, Minnesota

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Address

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, 55416

United Hospital, Saint Paul, Minnesota

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Address

United Hospital

Saint Paul, Minnesota, 55102

Ridgeview Medical Center, Waconia, Minnesota

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Address

Ridgeview Medical Center

Waconia, Minnesota, 55387

Woodbury, Minnesota

Status

Address

Minnesota Oncology Hematology PA-Woodbury

Woodbury, Minnesota, 55125

Washington University School of Medicine, Saint Louis, Missouri

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Address

Washington University School of Medicine

Saint Louis, Missouri, 63110

Billings, Montana

Status

Address

Northern Rockies Radiation Oncology Center

Billings, Montana, 59101

Keene, New Hampshire

Status

Address

Cheshire Medical Center-Dartmouth-Hitchcock Keene

Keene, New Hampshire, 03431

Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire

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Address

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756

John F Kennedy Medical Center, Edison, New Jersey

Status

Address

John F Kennedy Medical Center

Edison, New Jersey, 08818

Albuquerque, New Mexico

Status

Address

New Mexico Oncology Hematology Consultants

Albuquerque, New Mexico, 87109

Memorial Sloan-Kettering Cancer Center, New York, New York

Status

Address

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065

Highland Hospital, Rochester, New York

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Address

Highland Hospital

Rochester, New York, 14620

University of Rochester, Rochester, New York

Status

Address

University of Rochester

Rochester, New York, 14642

Mission Hospital-Memorial Campus, Asheville, North Carolina

Status

Address

Mission Hospital-Memorial Campus

Asheville, North Carolina, 28801

Charlotte, North Carolina

Status

Address

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203

Akron General Medical Center, Akron, Ohio

Status

Address

Akron General Medical Center

Akron, Ohio, 44307

Grandview Hospital, Dayton, Ohio

Status

Address

Grandview Hospital

Dayton, Ohio, 45405

Good Samaritan Hospital - Dayton, Dayton, Ohio

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Address

Good Samaritan Hospital - Dayton

Dayton, Ohio, 45406

Miami Valley Hospital, Dayton, Ohio

Status

Address

Miami Valley Hospital

Dayton, Ohio, 45409

Samaritan North Health Center, Dayton, Ohio

Status

Address

Samaritan North Health Center

Dayton, Ohio, 45415

Dayton, Ohio

Status

Address

Dayton NCI Community Oncology Research Program

Dayton, Ohio, 45420

Veteran Affairs Medical Center, Dayton, Ohio

Status

Address

Veteran Affairs Medical Center

Dayton, Ohio, 45428

Blanchard Valley Hospital, Findlay, Ohio

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Address

Blanchard Valley Hospital

Findlay, Ohio, 45840

Franklin, Ohio

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Address

Atrium Medical Center-Middletown Regional Hospital

Franklin, Ohio, 45005-1066

Kettering Medical Center, Kettering, Ohio

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Address

Kettering Medical Center

Kettering, Ohio, 45429

Upper Valley Medical Center, Troy, Ohio

Status

Address

Upper Valley Medical Center

Troy, Ohio, 45373

Greene Memorial Hospital, Xenia, Ohio

Status

Address

Greene Memorial Hospital

Xenia, Ohio, 45385

Legacy Mount Hood Medical Center, Gresham, Oregon

Status

Address

Legacy Mount Hood Medical Center

Gresham, Oregon, 97030

Providence Milwaukie Hospital, Milwaukie, Oregon

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Address

Providence Milwaukie Hospital

Milwaukie, Oregon, 97222

Portland, Oregon

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Address

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, 97210

Providence Portland Medical Center, Portland, Oregon

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Address

Providence Portland Medical Center

Portland, Oregon, 97213

Adventist Medical Center, Portland, Oregon

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Address

Adventist Medical Center

Portland, Oregon, 97216

Providence Saint Vincent Medical Center, Portland, Oregon

Status

Address

Providence Saint Vincent Medical Center

Portland, Oregon, 97225

Portland, Oregon

Status

Address

Legacy Emanuel Hospital and Health Center

Portland, Oregon, 97227

Legacy Meridian Park Hospital, Tualatin, Oregon

Status

Address

Legacy Meridian Park Hospital

Tualatin, Oregon, 97062

Radiation Therapy Oncology Group, Philadelphia, Pennsylvania

Status

Address

Radiation Therapy Oncology Group

Philadelphia, Pennsylvania, 19103

Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

Status

Address

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107

Rhode Island Hospital, Providence, Rhode Island

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Address

Rhode Island Hospital

Providence, Rhode Island, 02903

M D Anderson Cancer Center, Houston, Texas

Status

Address

M D Anderson Cancer Center

Houston, Texas, 77030

American Fork, Utah

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Address

American Fork Hospital / Huntsman Intermountain Cancer Center

American Fork, Utah, 84003

Sandra L Maxwell Cancer Center, Cedar City, Utah

Status

Address

Sandra L Maxwell Cancer Center

Cedar City, Utah, 84720

Cottonwood Hospital Medical Center, Murray, Utah

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Address

Cottonwood Hospital Medical Center

Murray, Utah, 84107

Intermountain Medical Center, Murray, Utah

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Address

Intermountain Medical Center

Murray, Utah, 84107

McKay-Dee Hospital Center, Ogden, Utah

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Address

McKay-Dee Hospital Center

Ogden, Utah, 84403

Utah Valley Regional Medical Center, Provo, Utah

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Address

Utah Valley Regional Medical Center

Provo, Utah, 84604

Saint George, Utah

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Address

Dixie Medical Center Regional Cancer Center

Saint George, Utah, 84770

Intermountain Health Care, Salt Lake City, Utah

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Address

Intermountain Health Care

Salt Lake City, Utah, 84103

Utah Cancer Specialists-Salt Lake City, Salt Lake City, Utah

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Address

Utah Cancer Specialists-Salt Lake City

Salt Lake City, Utah, 84106

LDS Hospital, Salt Lake City, Utah

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Address

LDS Hospital

Salt Lake City, Utah, 84143

Norris Cotton Cancer Center-North, Saint Johnsbury, Vermont

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Address

Norris Cotton Cancer Center-North

Saint Johnsbury, Vermont, 05819

Saint Francis Hospital, Federal Way, Washington

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Address

Saint Francis Hospital

Federal Way, Washington, 98003

EvergreenHealth Medical Center, Kirkland, Washington

Status

Address

EvergreenHealth Medical Center

Kirkland, Washington, 98033

Virginia Mason Medical Center, Seattle, Washington

Status

Address

Virginia Mason Medical Center

Seattle, Washington, 98101

University of Washington Medical Center, Seattle, Washington

Status

Address

University of Washington Medical Center

Seattle, Washington, 98195

PeaceHealth Southwest Medical Center, Vancouver, Washington

Status

Address

PeaceHealth Southwest Medical Center

Vancouver, Washington, 98664

Madison, Wisconsin

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Address

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792

Milwaukee, Wisconsin

Status

Address

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226