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Bevacizumab With or Without Radiation Therapy in Treating Patients With Recurrent Glioblastoma

Study Purpose

This randomized phase II trial studies how well bevacizumab with or without radiation therapy works in treating patients with recurrent glioblastoma. 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 cancer-killing substances to them. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is not yet know whether bevacizumab is more effective with or without radiation therapy in treating patients with recurrent glioblastoma

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:

  • - Histopathologically proven diagnosis of glioblastoma or variants (gliosarcoma, giant cell glioblastoma etc); patients will be eligible if the original histology was lower-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made.
  • - Patients who did not have recent surgery for their glioblastoma must have shown unequivocal radiographic evidence for tumor progression by contrast-enhanced magnetic resonance imaging (MRI) scan (or computed tomography [CT] scan for patients with non-compatible devices) CT scan within 21 days prior to registration.
* Note: Patients who did have surgery with a post-operative contrast-enhance scan falling outside the 5 week window prior to registration, must have a repeat MRI scan (or CT scan for patients with non-compatible devices) within 21 days prior to registration.
  • - Patients also must have passed an interval of 6 months or greater between completion of prior radiotherapy and registration; if patients have not passed an interval of at least 6 months, they may still be eligible if they meet one or more of the following criteria: - New areas of tumor outside the original radiotherapy fields as determined by the investigator, or.
  • - Histologic confirmation of tumor through biopsy or resection, or.
  • - Nuclear medicine imaging, magnetic resonance (MR) spectroscopy, or MR perfusion imaging consistent with true progressive disease, rather than radiation necrosis obtained within 28 days of registration AND an interval of at least 90 days between completion of radiotherapy and registration.
  • - Patients unable to undergo MR imaging because of non-compatible devices can be enrolled provided CT scans are obtained and are of sufficient quality; patients without non-compatible devices may not use CT scans performed to meet this requirement.
  • - Prior history of standard dose CNS radiation of 60 Gy in 30 fractions or 59.4 Gy in 1.8 Gy fractions, or equivalent or lower doses.
  • - Patients who have received prior treatment with non-standard radiation therapy (RT) dose and fractionation, interstitial brachytherapy, stereotactic radiosurgery, etc. are eligible.
  • - Patients must have recovered from the toxic effects of prior therapy, and there must be a minimum time of 28 days prior to registration from the administration of any investigational agent or prior cytotoxic therapy with the following exceptions: - 14 days from administration of vincristine.
  • - 42 days from administration of nitrosoureas.
  • - 21 days from administration of procarbazine.
  • - Patients having undergone recent resection of their glioblastoma (within 5 weeks prior to registration) must have recovered from the effects of surgery; for CNS related core or needle biopsies, a minimum of 7 days must have elapsed prior to registration.
  • - Residual disease following resection of recurrent glioblastoma is not mandated for eligibility into the study; to best assess the extent of residual disease post-operatively, a post-operative or intra-operative MRI scan (or CT scan for patients with non-compatible devices) must be performed prior to registration and should be within 96 hours post surgery (although 24 hours would be optimum) - History/physical examination, including neurologic examination, within 14 days prior to registration.
  • - Karnofsky performance status >= 60 within 14 days prior to registration.
  • - Complete blood count (CBC)/differential obtained within 14 days prior to registration, with adequate bone marrow function.
  • - Absolute neutrophil count (ANC) >= 1,500 cells/mm^3.
  • - Platelets >= 75,000 cells/mm^3.
  • - Hemoglobin >= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 9.0 g/dl is acceptable) - Total bilirubin =< 2.0 mg/dL.
  • - Serum glutamic oxaloacetic transaminase (SGOT) or aspartate aminotransferase (AST) =< 2.5 times the upper limit of normal.
  • - Serum creatinine =< 1.8 mg/dL.
  • - Urine protein creatinine (UPC) ratio >= 1.0 within 14 days prior to registration OR urine dipstick for proteinuria >= 2+ (patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate =< 1g of protein in 24 hours to be eligible) - Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm; UPC ratio is calculated using one of the following formulas: - [urine protein]/[urine creatinine]: if both protein and creatinine are reported in mg/dL.
  • - [(urine protein) x 0.088]/[urine creatinine]: if urine creatinine is reported in mmol/L.
  • - Patients must not be pregnant (positive pregnancy test) or breast feeding; pregnancy test must be done within 14 days prior to registration; effective contraception (men and women) must be used in patients of child-bearing potential while on trial and for 6 months after.
  • - Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight (LMW) heparin) must meet both of the following criteria: - No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices) - In-range international normalized ratio (INR) (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin, within 14 days prior to registration.
  • - Patient must be able to provide study-specific informed consent prior to study entry.

Exclusion Criteria:

  • - More than three relapses.
  • - Infratentorial or leptomeningeal evidence of recurrent disease.
  • - Recurrent or persistent tumor greater than 6 cm in maximum diameter.
  • - Prior therapy with an inhibitor of vascular endothelial growth factor (VEGF) or VEGFR (including bevacizumab) - Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1 year (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) - Severe, active co-morbidity, defined as follows: - Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration.
  • - Transmural myocardial infarction within the last 6 months prior to registration.
  • - History of stroke or transient ischemic attack within 6 months prior to registration.
  • - Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
  • - Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
  • - Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
  • - Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function other than screening panel and coagulation parameters are not required for entry into this protocol.
  • - Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive; protocol specific requirements may also exclude immuno-compromised patients.
  • - Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
  • - Prior allergic reaction to the study drug (bevacizumab) - Prior history of hypertensive crisis or hypertensive encephalopathy.
  • - History of a non-healing wound, ulcer, or bone fracture within 90 days (3 months) prior to registration.
  • - Gastrointestinal bleeding or any other hemorrhage/bleeding event Common Terminology Criteria for adverse Events (CTCAE), v.
4 grade 3 or greater within 30 days prior to registration. - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration (with the exception of craniotomy)

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.

NCT01730950
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.

Radiation Therapy Oncology Group
Principal Investigator

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

Christina TsienJeffrey Raizer, MDAdam P. Dicker, MD, PhDMartha M. Matuszak, PhD
Principal Investigator Affiliation Washington University School of MedicineNorthwestern UniversityJefferson Medical College of Thomas Jefferson UniversityUniversity of Michigan
Agency Class

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

Other, NIH
Overall Status Completed
Countries United States
Conditions

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

Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
Additional Details

PRIMARY OBJECTIVES:

  • I. To establish an improvement in overall survival in recurrent glioblastoma (GBM) patients receiving bevacizumab and re-irradiation compared with patients receiving bevacizumab alone.
SECONDARY OBJECTIVES:
  • I. To estimate and compare the rate of objective response in patients with measurable disease.
  • II. To estimate and compare the 6-month progression-free survival rate.
  • III. To estimate and compare progression-free survival.
  • IV. To estimate and compare the rate of treatment adverse events.
  • V. To estimate and compare the rate of grade 3+ acute or delayed central nervous system (CNS) toxicity.
OUTLINE: Patients are randomized to 1 of 2 treatment arms. In both arms, courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 1 year, every 6 months for 1 year and then annually thereafter.

Arms & Interventions

Arms

Active Comparator: Bevacizumab

Bevacizumab every 2 weeks

Experimental: Bevacizumab + RT

Radiation therapy with bevacizumab every 2 weeks

Interventions

Biological: - bevacizumab

Staring within 14 days of randomization, IV 10mg/kg every two weeks until disease progression.

Radiation: - radiation therapy

Starting with second dose of bevacizumab, 35 Gy in 10 fractions of 3.5 Gy each delivered on consecutive treatment days (typically 5 fractions per week).

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.

University of Alabama at Birmingham, Birmingham, Alabama

Status

Address

University of Alabama at Birmingham

Birmingham, Alabama, 35294

Arizona Oncology Services Foundation, Phoenix, Arizona

Status

Address

Arizona Oncology Services Foundation

Phoenix, Arizona, 85013

Arizona Oncology-Deer Valley Center, Phoenix, Arizona

Status

Address

Arizona Oncology-Deer Valley Center

Phoenix, Arizona, 85027

John Muir Medical Center, Walnut Creek, California

Status

Address

John Muir Medical Center

Walnut Creek, California, 94598

Yale University, New Haven, Connecticut

Status

Address

Yale University

New Haven, Connecticut, 06520-8032

Miami, Florida

Status

Address

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136

Queen's Medical Center, Honolulu, Hawaii

Status

Address

Queen's Medical Center

Honolulu, Hawaii, 96813

Radiation Oncology Associates PC, Fort Wayne, Indiana

Status

Address

Radiation Oncology Associates PC

Fort Wayne, Indiana, 46804

IU Health Methodist Hospital, Indianapolis, Indiana

Status

Address

IU Health Methodist Hospital

Indianapolis, Indiana, 46202

Memorial Hospital of South Bend, South Bend, Indiana

Status

Address

Memorial Hospital of South Bend

South Bend, Indiana, 46601

Norton Health Care Pavilion - Downtown, Louisville, Kentucky

Status

Address

Norton Health Care Pavilion - Downtown

Louisville, Kentucky, 40202

Maine Medical Center- Scarborough Campus, Scarborough, Maine

Status

Address

Maine Medical Center- Scarborough Campus

Scarborough, Maine, 04074

Lowell General Hospital, Lowell, Massachusetts

Status

Address

Lowell General Hospital

Lowell, Massachusetts, 01854

Ann Arbor, Michigan

Status

Address

University of Michigan University Hospital

Ann Arbor, Michigan, 48109

West Michigan Cancer Center, Kalamazoo, Michigan

Status

Address

West Michigan Cancer Center

Kalamazoo, Michigan, 49007

Washington University School of Medicine, Saint Louis, Missouri

Status

Address

Washington University School of Medicine

Saint Louis, Missouri, 63110

Nebraska Methodist Hospital, Omaha, Nebraska

Status

Address

Nebraska Methodist Hospital

Omaha, Nebraska, 68114

University of Rochester, Rochester, New York

Status

Address

University of Rochester

Rochester, New York, 14642

Cone Health Cancer Center, Greensboro, North Carolina

Status

Address

Cone Health Cancer Center

Greensboro, North Carolina, 27403

Summa Akron City Hospital, Akron, Ohio

Status

Address

Summa Akron City Hospital

Akron, Ohio, 44304

Summa Barberton Hospital, Barberton, Ohio

Status

Address

Summa Barberton Hospital

Barberton, Ohio, 44203

Lancaster General Hospital, Lancaster, Pennsylvania

Status

Address

Lancaster General Hospital

Lancaster, Pennsylvania, 17604

Radiation Therapy Oncology Group, Philadelphia, Pennsylvania

Status

Address

Radiation Therapy Oncology Group

Philadelphia, Pennsylvania, 19103

Pittsburgh, Pennsylvania

Status

Address

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212

Medical University of South Carolina, Charleston, South Carolina

Status

Address

Medical University of South Carolina

Charleston, South Carolina, 29425

University of Texas Medical Branch, Galveston, Texas

Status

Address

University of Texas Medical Branch

Galveston, Texas, 77555-0565

Yakima, Washington

Status

Address

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, 98902

Saint Vincent Hospital, Green Bay, Wisconsin

Status

Address

Saint Vincent Hospital

Green Bay, Wisconsin, 54301

Saint Mary's Hospital, Green Bay, Wisconsin

Status

Address

Saint Mary's Hospital

Green Bay, Wisconsin, 54303

Bay Area Medical Center, Marinette, Wisconsin

Status

Address

Bay Area Medical Center

Marinette, Wisconsin, 54143

Door County Cancer Center, Sturgeon Bay, Wisconsin

Status

Address

Door County Cancer Center

Sturgeon Bay, Wisconsin, 54235-1495