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

NCT01149850 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: 10-000760AVF4535s09-06-032
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

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.

Conditions

Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma

Keywords

adult giant cell glioblastoma; adult glioblastoma; adult gliosarcoma

Outcome Measures

Primary Outcomes (1)

• Overall survival

  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

  2 years

Secondary Outcomes (2)

• Time to progression

  2 years

• progression free survival

  2 years

Study Arms (1)

Arm I

EXPERIMENTAL

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; Drug: temozolomide; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: microarray analysis; Genetic: DNA methylation analysis

Interventions

bevacizumab BIOLOGICAL

Given IV

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

Arm I

temozolomide DRUG

Given orally

Also known as: CCRG-81045, M & B 39831, SCH 52365, Temodal, Temodar, TMZ

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Arm I

microarray analysis GENETIC

Correlative studies

Also known as: gene expression profiling

Arm I

DNA methylation analysis GENETIC

Correlative studies

Arm I

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (3)

Kaiser Foundation Hospital

Los Angeles, California, 90027, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Kaiser Permanente at San Diego

San Diego, California, 92120, United States

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Bevacizumab; Temozolomide; Immunohistochemistry; Microarray Analysis; Gene Expression Profiling; DNA Methylation

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Microchip Analytical Procedures; Genetic Techniques; Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena

Study Officials

• Phioanh Nghiemphu

  University of California at Los Angeles (UCLA )

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2010
• First Posted: June 24, 2010
• Study Start: April 28, 2010
• Primary Completion: December 8, 2023
• Study Completion: December 8, 2023
• Last Updated: September 19, 2024

Record last verified: 2024-02

Locations

US (3)