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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

Study 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. 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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.
  • - White Blood Cell (WBC) ≥ 3,000/mm³ - Absolute Neutrophil Count (ANC) ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - Hemoglobin ≥ 10 g/dL (transfusion allowed) - Serum Glutamate Oxaloacetate Transaminase (SGOT) < 2.5 times upper limit of normal (ULN) - Bilirubin < 2.5 times ULN.
  • - INR (international normalized ratio) ≤ 1.5 times ULN (except if on therapeutic anticoagulation therapy) - aPTT (activated partial thromboplastin time) ≤ 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 (port-a-cath - a port placed under the subjects skin), 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.
  • - New York Heart Association (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 (granulocyte-macrophage colony-stimulating factor) - concurrent stereotactic radiosurgery or brachytherapy.
  • - concurrent major surgical procedure.
- other concurrent anticancer therapy, including chemotherapy, hormonal therapy, radiotherapy, or immunotherapy

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT01013285
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Jonsson Comprehensive Cancer Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Albert Lai, MD
Principal Investigator Affiliation Ronald Reagan University of California, Los Angeles (UCLA) Medical Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Brain and Central Nervous System Tumors
Additional Details

OBJECTIVES: Primary.

  • - 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) Secondary.
  • - 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 vascular endothelial growth factor (VEGF)-dependent angiogenic pathways, gene expression microarray, and O-6 methylguanine DNA methyltransferase (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.

Arms & Interventions

Arms

Experimental: bevacizumab, temozolomide, external beam radiation

Interventions

Biological: - bevacizumab

Drug: - temozolomide

Radiation: - external beam radiation therapy

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Los Angeles, California

Status

Address

Jonsson Comprehensive Cancer Center, University of California, Los Angeles (UCLA)

Los Angeles, California, 90095-1781