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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Jonsson Comprehensive Cancer Center
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01149850
First received: June 22, 2010
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Giant Cell Glioblastoma
Glioblastoma
Gliosarcoma
Biological: bevacizumab
Drug: temozolomide
Other: laboratory biomarker analysis
Other: immunohistochemistry staining method
Genetic: microarray analysis
Genetic: DNA methylation analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Bevacizumab and Temozolomide in Elderly Patients With Newly-Diagnosed Glioblastoma

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Time to progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 50
Study Start Date: April 2010
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

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.

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01149850

Locations
United States, California
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Phioanh Nghiemphu, M.D.    310-825-5321      
Principal Investigator: Phioanh Nghiemphu         
Kaiser Foundation Hospital Recruiting
Los Angeles, California, United States, 90027
Contact: Richard M. Green    323-783-7181      
Principal Investigator: Richard M. Green         
Kaiser Permanente at San Diego Recruiting
San Diego, California, United States, 92120
Contact: Jonathan A. Polikoff    619-641-2675      
Principal Investigator: Jonathan A. Polikoff         
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Genentech
Investigators
Principal Investigator: Phioanh Nghiemphu University of California at Los Angeles (UCLA )
  More Information

No publications provided

Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01149850     History of Changes
Other Study ID Numbers: AVF4535s, 09-06-032
Study First Received: June 22, 2010
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Jonsson Comprehensive Cancer Center:
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Temozolomide
Dacarbazine
Antibodies
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014