Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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.
 
ClinicalTrials.gov 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
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE November 11, 2009
First Posted Date  ICMJE November 13, 2009
Last Update Posted Date January 21, 2016
Study Start Date  ICMJE June 2006
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 22, 2013)
Overall survival [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 11, 2009)
  • Overall survival
  • Toxicity as assessed by NCI CTCAE v3.0
Change History Complete list of historical versions of study NCT01013285 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2013)
  • Time to disease progression [ Time Frame: 2 years ]
  • Progression-free survival at 6 months [ Time Frame: 6 months ]
  • Radiographic response (when evaluable) [ Time Frame: 2 years ]
  • Correlation of clinical response with VEGF pathway profiling, gene expression microarray, and MGMT methylation [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2009)
  • Time to disease progression
  • Progression-free survival at 6 months
  • Radiographic response (when evaluable)
  • Correlation of clinical response with VEGF pathway profiling, gene expression microarray, and MGMT methylation
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bevacizumab, Temozolomide, and External Beam Radiation Therapy as First-Line Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma
Official Title  ICMJE Phase II Trial of Bevacizumab in Combination With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly-diagnosed Glioblastoma Multiforme
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE
  • Biological: bevacizumab
  • Drug: temozolomide
  • Radiation: external beam radiation therapy
Study Arms  ICMJE Experimental: bevacizumab, temozolomide, external beam radiation
Interventions:
  • Biological: bevacizumab
  • Drug: temozolomide
  • Radiation: external beam radiation therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: November 11, 2009)
70
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2017
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01013285
Other Study ID Numbers  ICMJE CDR0000628787
P30CA016042 ( U.S. NIH Grant/Contract )
UCLA-0604016
AVF3770s
IRB#06-04-016-03B
GENENTECH-UCLA-0604016
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jonsson Comprehensive Cancer Center
Study Sponsor  ICMJE Jonsson Comprehensive Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Albert Lai, MD Ronald Reagan UCLA Medical Center
PRS Account Jonsson Comprehensive Cancer Center
Verification Date January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP