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Adult Giant Cell GlioblastomaPhase 2NCT01730950

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

A Phase 2 study testing bevacizumab and radiation therapy in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by Radiation Therapy Oncology Group at 31 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
bevacizumab and radiation therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
182 participants
Where
31 sitesUnited States
Study dates
20 Dec 2012to 22 Dec 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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:
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  • 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 locations and contacts

31 sites in 1 country.

31 sites in 1 country

United States31 sites

  • Summa Akron City Hospital

    Akron, Ohio, 44304

  • University of Michigan University Hospital

    Ann Arbor, Michigan, 48109

  • Summa Barberton Hospital

    Barberton, Ohio, 44203

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Radiation Oncology Associates PC

    Fort Wayne, Indiana, 46804

  • University of Texas Medical Branch

    Galveston, Texas, 77555-0565

  • Saint Vincent Hospital

    Green Bay, Wisconsin, 54301

  • Saint Mary's Hospital

    Green Bay, Wisconsin, 54303

  • Cone Health Cancer Center

    Greensboro, North Carolina, 27403

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • IU Health Methodist Hospital

    Indianapolis, Indiana, 46202

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Lancaster General Hospital

    Lancaster, Pennsylvania, 17604

  • Norton Health Care Pavilion - Downtown

    Louisville, Kentucky, 40202

  • Lowell General Hospital

    Lowell, Massachusetts, 01854

  • Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Yale University

    New Haven, Connecticut, 06520-8032

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • Radiation Therapy Oncology Group

    Philadelphia, Pennsylvania, 19103

  • Arizona Oncology Services Foundation

    Phoenix, Arizona, 85013

  • Arizona Oncology-Deer Valley Center

    Phoenix, Arizona, 85027

  • Allegheny Cancer Center at Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • University of Rochester

    Rochester, New York, 14642

  • Maine Medical Center- Scarborough Campus

    Scarborough, Maine, 04074

  • Memorial Hospital of South Bend

    South Bend, Indiana, 46601

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Door County Cancer Center

    Sturgeon Bay, Wisconsin, 54235-1495

  • John Muir Medical Center

    Walnut Creek, California, 94598

  • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

    Yakima, Washington, 98902

Other trials in United States

About this study

Official title: Randomized Phase II Trial of Concurrent Bevacizumab and Re-Irradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
bevacizumab, radiation therapy
Medical subject headings
Glioblastoma, Gliosarcoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bevacizumabBiological

    Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

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

  • radiation therapyRadiation

    Also called 3D conformal radiation therapy, photon beam radiation therapy, proton beam radiation therapy, Intensity Modulated Radiation Therapy (IMRT)

    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).

Study groups in NCT01730950
Study groupRoleWhat they receive
BevacizumabActive comparatorBevacizumab every 2 weeks
Receives: Biological: bevacizumab
Bevacizumab + RTExperimentalRadiation therapy with bevacizumab every 2 weeks
Receives: Biological: bevacizumab; Radiation: radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (5)

  1. Percentage of Participants With Complete or Partial Best Response

    Best observed objective response determined by serial measures of the product of the two largest perpendicular cross-sectional diameters using MacDonald Criteria:

    • Complete Response (CR): complete disappearance of measurable enhancing lesion sustained ≥ 4 weeks; and no new lesions; and no corticosteroids.
    • Partial Response (PR): ≥ 50% decrease from baseline in sum of products of the measurable enhancing lesion sustained ≥ 4 weeks; and no new lesions; and stable/reduced corticosteroid dose.
    • Progression (P): ≥ 25% increase in sum of products of enhancing lesions (patient has not had steroid dose decreased since the last evaluation period); or any new lesions. A concomitant decrease in steroid dose rules out progression designation during initial 12 weeks after radiotherapy.
    • Stable Disease (SD): all of following: does not qualify for CR, PR, or P; receiving stable/decreasing doses of steroids.

    Estimated using an exact binomial distribution.

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

  2. Percentage of Participants Progression-free at 6 Months

    Best observed objective response determined by serial measures of the product of the two largest perpendicular cross-sectional diameters using MacDonald Criteria:

    Progression (P): ≥ 25% increase in sum of products of enhancing lesions (patient has not had steroid dose decreased since the last evaluation period); or any new lesions. A concomitant decrease in steroid dose rules out progression designation during initial 12 weeks after radiotherapy. Progression-free at 6 months means patient alive without progression at 6 months.

    Measured: From randomization to six months

  3. Progression-free Survival

    Progression using using MacDonald Criteria is defined as ≥ 25% increase from baseline in sum of products of the two largest perpendicular cross-sectional diameters of enhancing lesions (patient has not had steroid dose decreased since the last evaluation period); or any new lesions. A concomitant decrease in steroid dose rules out progression designation during initial 12 weeks after radiotherapy. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using 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.

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

  4. 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

    Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.

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

  5. 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

    Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Estimated using an exact binomial distribution together with 95% confidence interval. The difference between the two groups will be tested using a chi square test.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Nov 2012 (estimated)
  2. Study start20 Dec 2012
  3. Primary completion3 Sep 2018
  4. Study completion22 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
182 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01730950
Sponsor's protocol ID
RTOG-1205
Other IDs
NCI-2012-01732, U10CA021661
Status last verified
Dec 2022
First submitted
15 Nov 2012
Last updated
29 Dec 2022
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 36260832

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bevacizumab and radiation therapy in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by Radiation Therapy Oncology Group at 31 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01730950, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2022.

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