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Bevacizumab and Temozolomide in Treating Older Patients With Newly-Diagnosed Glioblastoma Multiforme or Gliosarcoma

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: NCT01149850
Recruitment Status : Active, not recruiting
First Posted : June 24, 2010
Last Update Posted : February 27, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE June 22, 2010
First Posted Date  ICMJE June 24, 2010
Last Update Posted Date February 27, 2019
Actual Study Start Date  ICMJE April 28, 2010
Estimated Primary Completion Date January 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2012)
Overall survival [ Time Frame: 2 years ]
Pts who progress followed for survival every 4 mths.Pts completing therapy & no progression followed every 2 mths/12 mths,every 3 mths/12 mths,every 4 mths/12 mths,every 6 mths until progression,then followed every 4 mths for survival
Original Primary Outcome Measures  ICMJE
 (submitted: June 23, 2010)
Overall survival [ Time Frame: At 6 months ]
Change History Complete list of historical versions of study NCT01149850 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2012)
  • Time to progression [ Time Frame: 2 years ]
    Pts who progress followed for survival every 4 mths.Pts completing therapy & no progression followed every 2 mths/12 mths,every 3 mths/12 mths,every 4 mths/12 mths,every 6 mths until progression.
  • progression free survival [ Time Frame: 2 years ]
    Patients completing therapy & no progression followed every 2 mths/12 mths,every 3 mths/12 mths,every 4 mths/12 mths,every 6 mths until progression,then followed every 4 mths for survival
Original Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2010)
  • Survival [ Time Frame: At 12 months ]
  • Time to progression
  • progression free survival
  • Radiographic response (when evaluable)
  • Correlation of clinical response with VEGF pathway profiling
  • Gene expression microarray
  • MGMT methylation
  • Toxicity as assessed by CTC version 3.0
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bevacizumab and Temozolomide in Treating Older Patients With Newly-Diagnosed Glioblastoma Multiforme or Gliosarcoma
Official Title  ICMJE Phase II Study of Bevacizumab and Temozolomide in Elderly Patients With Newly-Diagnosed Glioblastoma
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. Drugs used in chemotherapy, such as temozolomide, also work in different ways to kill tumor cells or stop them from growing. Giving bevacizumab together with temozolomide may be a better way to block tumor growth.

PURPOSE: This phase II trial is studying how well giving bevacizumab and temozolomide together works in treating older patients with newly diagnosed glioblastoma multiforme or gliosarcoma.

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate overall survival in elderly subjects treated with bevacizumab and temozolomide for newly diagnosed glioblastoma multiforme.

SECONDARY OBJECTIVES:

I. To estimate 12-months survival. II. To estimate progression free survival for 2 years or until progression is detected.

III. To investigate the safety and tolerability of bevacizumab/temozolomide in elderly patient with glioblastoma.

IV. To isolate DNA, RNA, and protein isolated from frozen and paraffinized archival tumor samples for evaluations such as immunohistochemical pathway profiling of VEGF-dependent angiogenic pathways, gene expression microarray, and MGMT promoter methylation status to define important molecule features of treatment response and especially age-related molecular expression.

OUTLINE:

Patients receive bevacizumab IV over 30-90 minutes every 2 weeks and oral temozolomide on days 1-5. Treatment repeats every 28 days for 24 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at least every 4 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Giant Cell Glioblastoma
  • Glioblastoma
  • Gliosarcoma
Intervention  ICMJE
  • Biological: bevacizumab
    Given IV
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • anti-VEGF rhuMAb
    • Avastin
    • recombinant humanized anti-VEGF monoclonal antibody
    • rhuMAb VEGF
  • Drug: temozolomide
    Given orally
    Other Names:
    • CCRG-81045
    • M & B 39831
    • SCH 52365
    • Temodal
    • Temodar
    • TMZ
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: immunohistochemistry staining method
    Correlative studies
    Other Name: immunohistochemistry
  • Genetic: microarray analysis
    Correlative studies
    Other Name: gene expression profiling
  • Genetic: DNA methylation analysis
    Correlative studies
Study Arms  ICMJE Experimental: Arm I
Patients receive bevacizumab IV over 30-90 minutes every 2 weeks and oral temozolomide on days 1-5. Treatment repeats every 28 days for 24 courses in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Biological: bevacizumab
  • Drug: temozolomide
  • Other: laboratory biomarker analysis
  • Other: immunohistochemistry staining method
  • Genetic: microarray analysis
  • Genetic: DNA methylation analysis
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 23, 2010)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2021
Estimated Primary Completion Date January 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients will have histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS); this includes treatment-naive patients with prior tissue diagnosis of lower grade gliomas that have been upgraded after repeat resection
  • Cranial MRI or contrast CT must have been performed within 21 days of study entry; the use of MRI rather than CT is preferred; the same type of scan, i.e., MRI or CT, must be used throughout the period of protocol treatment for tumor measurement; if the surgical procedure was a resection, cranial MRI or contrast CT performed within 96 hours of resection is preferred, but not required; patients without measureable or assessable disease are eligible
  • Patients must begin temozolomide chemotherapy no sooner than 2 weeks and no later than 6 weeks from the diagnostic surgery; patients must begin bevacizumab no sooner than 4 weeks and no later than 6 weeks from the surgery
  • Patients must be willing to forego other drug therapy against the tumor while being treated with bevacizumab and temozolomide
  • All patients must sign and informed consent approved by the Institutional Review Board indicating that they are aware of the investigational nature of this study; patients must also sign an authorization for the release of their protected heath information
  • Life expectancy > 8 weeks
  • Patients must have a Karnofsky performance status of >= 60
  • WBC >= 3,000/ul
  • ANC >= 1,500/mm^3
  • Platelet count of >= 100,000/mm^3
  • Hemoglobin >= 10 gm/dl
  • SGOT < 2.5 times ULN
  • Bilirubin < 2.5 ULN
  • Patients must have adequate renal function (creatinine < 1.5 mg/dL) before starting therapy and the test must be performed within 14 days prior to registration

Exclusion Criteria:

  • Glioblastoma disease-specific concerns: Patients must not have received previous or concurrent radiotherapy to the brain
  • Glioblastoma disease-specific concerns: Patients must have received cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor; patients who received Gliadel wafers will be excluded; patients may have received or be receiving corticosteroids, AED's, analgesics, and other drugs to treat symptoms or prevent complications
  • Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
  • Patients with a history of any other cancer (except non-melanoma skin cancer, carcinoma in-situ of the cervix, or low-risk prostate cancer after curative therapy), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible
  • Patients receiving current, ongoing treatment with full-dose warfarin or its equivalent (i.e., unfractionated and/or low molecular weight heparin) are NOT excluded
  • Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism
  • Patients must not have serious uncontrolled inter-current medical illness including, but not limited to, ongoing or active infection requiring IV antibiotics, psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state (HIV, SLE, etc.)
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
  • Blood pressure of > 150/100 mmHg, history of hypertensive crisis or hypertensive encephalopathy
  • Unstable angina
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of myocardial infarction within 6 months prior to day 1
  • History of stroke within 6 months prior to day 1
  • International normalized ratio (INR) > 1.5 and activated partial thromboplastin time (aPTT) > 1.5 x the ULN (except for subjects receiving anticoagulation therapy) in the absence of therapeutic intent to anticoagulate the subject; therapeutic anticoagulation is permitted
  • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
  • History of hemoptysis ( >= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Major surgical procedure, open biopsy, or significant traumatic injury other than craniotomy within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study
  • Minor surgical procedures such as placement of Port-a-Cath, stereotactic biopsy, fine needle aspirations, or core biopsies within 7 days prior to Day 1
  • History of intracerebral abscess within 6 months prior to Day 1
  • Urine protein: creatinine ratio >= 1.0 at screening
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
  • Serious, non-healing wound, ulcer, or bone fracture; patients with any wound requiring surgical intervention (including scalp wounds requiring cranioplasty) will be allowed to resume the study if the wound is clean and without further infection post-surgical intervention
  • Known hypersensitivity to any component of bevacizumab
  • Inability to comply with study and/or follow-up procedures
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 70 Years and older   (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 NCT01149850
Other Study ID Numbers  ICMJE AVF4535s
10-000760 ( Other Identifier: UCLA IRB )
09-06-032 ( Other Identifier: UCLA IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jonsson Comprehensive Cancer Center
Study Sponsor  ICMJE Jonsson Comprehensive Cancer Center
Collaborators  ICMJE Genentech, Inc.
Investigators  ICMJE
Principal Investigator: Phioanh Nghiemphu University of California at Los Angeles (UCLA )
PRS Account Jonsson Comprehensive Cancer Center
Verification Date February 2019

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