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

NCT01730950 | Completed Phase 2 Results DMC

• 3 other identifiers: RTOG-1205NCI-2012-01732U10CA021661
• Study Type: interventional
• Target: 182
• Locations: 1 country
• Sites: 31

Brief Summary

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

Conditions

Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times will be compared between the arms, which is reported in the statistical analysis results. Eighteen-month rates are provided. Analysis was planned to occur when 135 deaths were reported.

  From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.

Secondary Outcomes (5)

• Percentage of Participants With Complete or Partial Best Response

  From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.

• Percentage of Participants Progression-free at 6 Months

  From randomization to six months

• Progression-free Survival

  From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.

• Percentage of Participants With Grade 3+ Central Nervous System (CNS) Toxicity Within 90 Days of Start of Radiation Therapy Reported as Possibly/Probably/Definitely Related to Protocol Treatment

  From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.

• Number of Participants With Grade 3+ CNS Toxicity More Than 90 Days of Start of Radiation Therapy Reported as Possibly/Probably/Definitely Related to Protocol Treatment

  From 91 days after the start of radiation therapy to end of follow-up. Maximum follow-up at the time of analysis is 58.2 months.

Study Arms (2)

Bevacizumab

ACTIVE COMPARATOR

Bevacizumab every 2 weeks

Biological: bevacizumab

Bevacizumab + RT

EXPERIMENTAL

Radiation therapy with bevacizumab every 2 weeks

Biological: bevacizumab; Radiation: radiation therapy

Interventions

bevacizumab BIOLOGICAL

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

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Bevacizumab; Bevacizumab + RT

radiation therapy RADIATION

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).

Also known as: 3D conformal radiation therapy, photon beam radiation therapy, proton beam radiation therapy, Intensity Modulated Radiation Therapy (IMRT), Image-Guided Radiation Treatment (IGRT), 3D-CRT

Bevacizumab + RT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• days from administration of vincristine
• days from administration of nitrosoureas
• 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

You may not qualify if:

• 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
• Prior allergic reaction to the study drug (bevacizumab)

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (31)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Arizona Oncology Services Foundation

Phoenix, Arizona, 85013, United States

Location

Arizona Oncology-Deer Valley Center

Phoenix, Arizona, 85027, United States

Location

John Muir Medical Center

Walnut Creek, California, 94598, United States

Location

Yale University

New Haven, Connecticut, 06520-8032, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

Radiation Oncology Associates PC

Fort Wayne, Indiana, 46804, United States

Location

IU Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

Norton Health Care Pavilion - Downtown

Louisville, Kentucky, 40202, United States

Location

Maine Medical Center- Scarborough Campus

Scarborough, Maine, 04074, United States

Location

Lowell General Hospital

Lowell, Massachusetts, 01854, United States

Location

University of Michigan University Hospital

Ann Arbor, Michigan, 48109, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Cone Health Cancer Center

Greensboro, North Carolina, 27403, United States

Location

Summa Akron City Hospital

Akron, Ohio, 44304, United States

Location

Summa Barberton Hospital

Barberton, Ohio, 44203, United States

Location

Lancaster General Hospital

Lancaster, Pennsylvania, 17604, United States

Location

Radiation Therapy Oncology Group

Philadelphia, Pennsylvania, 19103, United States

Location

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0565, United States

Location

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, 98902, United States

Location

Saint Vincent Hospital

Green Bay, Wisconsin, 54301, United States

Location

Saint Mary's Hospital

Green Bay, Wisconsin, 54303, United States

Location

Bay Area Medical Center

Marinette, Wisconsin, 54143, United States

Location

Door County Cancer Center

Sturgeon Bay, Wisconsin, 54235-1495, United States

Location

Related Publications (1)

• Tsien CI, Pugh SL, Dicker AP, Raizer JJ, Matuszak MM, Lallana EC, Huang J, Algan O, Deb N, Portelance L, Villano JL, Hamm JT, Oh KS, Ali AN, Kim MM, Lindhorst SM, Mehta MP. NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma. J Clin Oncol. 2023 Feb 20;41(6):1285-1295. doi: 10.1200/JCO.22.00164. Epub 2022 Oct 19.

  PMID: 36260832 DERIVED

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

Bevacizumab; Radiotherapy; Radiotherapy, Conformal; Proton Therapy; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Radiotherapy, Computer-Assisted; Heavy Ion Radiotherapy

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

215-574-3208

Study Officials

• Christina Tsien

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Jeffrey Raizer, MD

  Northwestern University

  STUDY CHAIR

• Adam P. Dicker, MD, PhD

  Jefferson Medical College of Thomas Jefferson University

  STUDY CHAIR

• Martha M. Matuszak, PhD

  University of Michigan

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2012
• First Posted: November 21, 2012
• Study Start: December 20, 2012
• Primary Completion: September 3, 2018
• Study Completion: December 22, 2022
• Last Updated: December 29, 2022
• Results First Posted: March 17, 2020

Record last verified: 2022-12

Locations

US (31)