Bevacizumab, Temozolomide, and External Beam Radiation Therapy as First-Line Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01013285
First received: November 11, 2009
Last updated: September 8, 2014
Last verified: September 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. 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 Intervention Phase
Brain and Central Nervous System Tumors
Biological: bevacizumab
Drug: temozolomide
Radiation: external beam radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

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 ]

Secondary Outcome Measures:
  • Time to disease progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Progression-free survival at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Radiographic response (when evaluable) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Correlation of clinical response with VEGF pathway profiling, gene expression microarray, and MGMT methylation [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: June 2006
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bevacizumab, temozolomide, external beam radiation Biological: bevacizumab Drug: temozolomide Radiation: external beam radiation therapy

Detailed Description:

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  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: NCT01013285

Locations
United States, California
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Albert Lai, MD Ronald Reagan UCLA Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01013285     History of Changes
Other Study ID Numbers: CDR0000628787, P30CA016042, UCLA-0604016, AVF3770s, IRB#06-04-016-03B, GENENTECH-UCLA-0604016
Study First Received: November 11, 2009
Last Updated: September 8, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on September 18, 2014