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Bevacizumab, Temozolomide, and External Beam Radiation Therapy as First-Line Therapy in Treating 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. Identifier: NCT01013285
Recruitment Status : Unknown
Verified January 2016 by Jonsson Comprehensive Cancer Center.
Recruitment status was:  Active, not recruiting
First Posted : November 13, 2009
Last Update Posted : January 21, 2016
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

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 temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x-rays to kill tumor cells. Giving bevacizumab together with temozolomide and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving bevacizumab together with temozolomide and external beam radiation therapy works when given as first-line therapy in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Biological: bevacizumab Drug: temozolomide Radiation: external beam radiation therapy Phase 2

Detailed Description:



  • To investigate the safety and tolerability of bevacizumab in combination with temozolomide and external beam fractionated regional radiotherapy as first-line treatment in patients with newly diagnosed glioblastoma multiforme or gliosarcoma. (Pilot phase)
  • To estimate the overall survival of patients treated with this regimen. (Expansion phase)


  • To further investigate the safety and tolerability of this regimen in these patients. (Expansion phase)
  • To isolate DNA, RNA, and protein from frozen and paraffin-embedded 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 molecular features of treatment response.

OUTLINE: This is a multicenter study.

Patients undergo external beam fractionated regional radiotherapy once daily 5 days a week for 6 weeks and receive concurrent oral temozolomide once daily for 6 weeks. Patients also receive bevacizumab IV over 30-90 minutes every 2 weeks beginning on the first day of radiotherapy and continuing in the absence of disease progression or unacceptable toxicity. Beginning 2-5 weeks after completion of radiotherapy, patients receive oral temozolomide on days 1-5. Treatment with temozolomide repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Blood and frozen and paraffin-embedded tumor tissue samples are collected for biomarker and genetic analysis.

After completion of study treatment, patients are followed up periodically.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Bevacizumab in Combination With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly-diagnosed Glioblastoma Multiforme
Study Start Date : June 2006
Actual Primary Completion Date : October 2013
Estimated Study Completion Date : January 2017

Arm Intervention/treatment
Experimental: bevacizumab, temozolomide, external beam radiation Biological: bevacizumab
Drug: temozolomide
Radiation: external beam radiation therapy

Primary Outcome Measures :
  1. Overall survival [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Time to disease progression [ Time Frame: 2 years ]
  2. Progression-free survival at 6 months [ Time Frame: 6 months ]
  3. Radiographic response (when evaluable) [ Time Frame: 2 years ]
  4. Correlation of clinical response with VEGF pathway profiling, gene expression microarray, and MGMT methylation [ Time Frame: 2 years ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed intracranial glioblastoma multiforme (GBM) or gliosarcoma.
  • Prior histologic diagnosis of low-grade glioma allowed provided it has been upgraded to GBM after repeat resection
  • Has undergone surgery to collect tumor tissue 3-6 weeks ago
  • Measurable or assessable disease is not required
  • Karnofsky performance status 60-100%
  • Life expectancy > 8 weeks
  • WBC ≥ 3,000/mm³
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10 g/dL (transfusion allowed)
  • SGOT < 2.5 times upper limit of normal (ULN)
  • Bilirubin < 2.5 times ULN
  • INR ≤ 1.5 times ULN (except if on therapeutic anticoagulation therapy)
  • aPTT ≤ 1.5 times ULN (except if on therapeutic anticoagulation therapy)
  • Creatinine < 1.5 mg/dL
  • Urine protein:creatinine ratio < 1.0
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • More than 28 days since prior major surgical procedures or open biopsy (other than craniotomy)
  • More than 7 days since prior minor surgical procedures (e.g., placement of PortoCath, stereotactic biopsy, fine-needle aspirations, or core biopsies)
  • More than 4 weeks since prior and no concurrent participation in another experimental drug study.
  • Prior or concurrent corticosteroids, anti-epileptic drugs, analgesics, or other drugs to treat symptoms or prevent complications are allowed
  • Concurrent full-dose warfarin or its equivalent (i.e., unfractionated and/or low molecular weight heparin) allowed

Exclusion Criteria:

  • unstable angina
  • BP > 150/100 mm Hg
  • NYHA class II-IV congestive heart failure
  • myocardial infarction within the past 6 months
  • stroke within the past 6 months
  • clinically significant peripheral vascular disease
  • evidence of bleeding diathesis or coagulopathy
  • intracerebral abscess within past 6 months
  • abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • serious, non-healing wound, ulcer, or bone fracture
  • Any wound requiring surgical intervention (including scalp wounds requiring cranioplasty) allowed provided the wound is clean and without further infection post-surgical intervention
  • significant traumatic injury within the past 28 days
  • concurrent serious uncontrolled medical illness including, but not limited to, the following:
  • Ongoing or active infection requiring IV antibiotics
  • Psychiatric illness/social situation that would limit compliance with study requirements
  • Disorders associated with significant immunocompromised state (e.g., HIV, systemic lupus erythematosus)
  • other cancer within the past 3 years, except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • disease that would obscure toxicity or dangerously alter drug metabolism
  • significant medical illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate study therapy
  • prior radiotherapy to the brain
  • prior cytotoxic or non-cytotoxic drug therapy or experimental drug therapy for the brain tumor
  • prior Gliadel wafers
  • concurrent participation in any other clinical trial
  • concurrent GM-CSF
  • concurrent stereotactic radiosurgery or brachytherapy
  • concurrent major surgical procedure
  • other concurrent anticancer therapy, including chemotherapy, hormonal therapy, radiotherapy, or immunotherapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01013285

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United States, California
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
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Principal Investigator: Albert Lai, MD Ronald Reagan UCLA Medical Center

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Responsible Party: Jonsson Comprehensive Cancer Center Identifier: NCT01013285    
Other Study ID Numbers: CDR0000628787
P30CA016042 ( U.S. NIH Grant/Contract )
First Posted: November 13, 2009    Key Record Dates
Last Update Posted: January 21, 2016
Last Verified: January 2016
Keywords provided by Jonsson Comprehensive Cancer Center:
adult giant cell glioblastoma
adult gliosarcoma
adult glioblastoma
Additional relevant MeSH terms:
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Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action