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Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00795665
Recruitment Status : Completed
First Posted : November 21, 2008
Results First Posted : May 12, 2020
Last Update Posted : May 12, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Genentech, Inc.
Information provided by (Responsible Party):
University of California, Davis

Tracking Information
First Submitted Date  ICMJE November 20, 2008
First Posted Date  ICMJE November 21, 2008
Results First Submitted Date  ICMJE July 3, 2018
Results First Posted Date  ICMJE May 12, 2020
Last Update Posted Date May 12, 2020
Study Start Date  ICMJE June 2008
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 4, 2020)
Progression-free Survival [ Time Frame: Time from first day of treatment to the first observation of disease progression or death due to any cause (up to 7 years). ]
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2008)
  • Progression-free Survival
  • Overall survival
  • Response rate
  • Time to disease progression
  • Safety and toxicity as measured by NCI CTCAE v3.0 criteria
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2020)
  • Radiographic Response to Therapy [ Time Frame: One year ]
    Response measured using MRI and PET with image fusion
  • Differentiate a Radiographic Response Due to Tumor Shrinkage From a Radiographic Response Due to Decreased Vasogenic Edema [ Time Frame: One year ]
    Measurements made by novel brain imaging
  • Safety and Toxicity [ Time Frame: One year ]
    Subjects will be assessed clinically for toxicity prior to, during, and after each infusion. NCI CTCAE 3.0 Common Terminology Criteria (CTC) for Adverse Events for toxicity and Adverse Event Reporting will be utilized.
  • Overall Survival [ Time Frame: Time from first day of treatment to time of death due to any cause (up to 7 years). ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma
Official Title  ICMJE Phase II Study of Bevacizumab (Avastin) and BCNU for Treatment of Relapsed, High Grade Gliomas
Brief Summary

RATIONALE: 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 carmustine, 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 carmustine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with carmustine works in treating patients with relapsed or progressive high-grade glioma.

Detailed Description

OBJECTIVES:

Primary

  • To determine the 6-month progression-free survival of patients with relapsed or progressive high-grade gliomas treated with bevacizumab and carmustine.

Secondary

  • To evaluate the radiographic response to this regimen as measured by MRI and PET scan with image fusion.
  • To utilize novel brain imaging to differentiate between a radiographic response due to tumor shrinkage and a radiographic response due to decreased vasogenic edema.
  • To evaluate the safety and toxicity of this regimen in these patients.
  • To evaluate the overall survival of these patients.

OUTLINE: Patients receive bevacizumab IV on days -7, 8, 22, 36, and 50 of course 1 and on days 8, 22, 36, and 50 of all subsequent courses. Patients also receive carmustine IV over 4 hours on day 1. Treatment repeats every 56 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioma
Intervention  ICMJE
  • Drug: bevacizumab
    Bevacizumab (10 mg/kg) will be given intravenously every other week starting one week before the first dose of BCNU. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU.
    Other Name: Avastin
  • Drug: carmustine
    BCNU (200 mg/m2), will be given over 4 hours as a continuous intravenous infusion every 8 weeks. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU.
    Other Name: BCNU
Study Arms  ICMJE Experimental: Bevacizumab and Carmustine
Interventions:
  • Drug: bevacizumab
  • Drug: carmustine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 4, 2016)
7
Original Estimated Enrollment  ICMJE
 (submitted: November 20, 2008)
20
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed GBM, anaplastic astrocytoma, anaplastic oligoastrocytoma or anaplastic oligodendroglioma.
  • Disease progression (confirmed by MRI, PET or both) after radiation therapy
  • At least 28 days have elapsed since chemotherapy, major surgery or radiation therapy.
  • No other malignancy within 3 years except for non-melanomatous skin cancer or in situ cervical cancer.
  • Karnofsky performance score at least 70
  • Platelet count ≥ 130/mm3.
  • Absolute neutrophil count ≥ 1500/mm3
  • Calculated creatinine clearance greater than 45 mg/dl
  • AST < 2 times the upper limit of normal
  • Bilirubin < 1.5 times the upper limit of normal
  • Ability to give signed informed consent
  • Patients must be 18 years of age or older.

Exclusion Criteria:

  • Prior intravenous or oral nitrosoureas (BCNU, CCNU) or prior VEGF targeted therapy including bevacizumab. No more than two prior chemotherapy regimens are allowed. Prior or current steroid use is allowed.
  • Evidence of CNS hemorrhage
  • Requirement for therapeutic anticoagulation
  • Any grade 3 or greater hemorrhage within the previous 28 days
  • Active inflammatory bowel disease
  • Inadequately controlled hypertension
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association Grade II or greater congestive heart failure
  • History of myocardial infarction or unstable angina within 6 months prior to study enrollment
  • History of stroke or transient ischemic attack within 6 months prior to study enrollment
  • Significant vascular disease
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Serious, non-healing wound, ulcer, or bone fracture
  • Proteinuria at screening
  • Pregnant (or lactating). Use of effective means of contraception in subjects of child-bearing potential
  • Prior organ transplantation
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Known acquired immune deficiency syndrome (AIDS) or HIV positive status
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00795665
Other Study ID Numbers  ICMJE 224865
UCDCC#208 ( Other Identifier: UC Davis )
P30CA093373 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of California, Davis
Study Sponsor  ICMJE University of California, Davis
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Genentech, Inc.
Investigators  ICMJE
Principal Investigator: Robert T. O'Donnell, MD, PhD University of California, Davis
PRS Account University of California, Davis
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP