Bevacizumab and Erlotinib After Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma
- Conditions
- Brain and Central Nervous System Tumors
- Interventions
- Registration Number
- NCT00720356
- Lead Sponsor
- Northwestern University
- 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. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bevacizumab together with erlotinib may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib works after radiation therapy and temozolomide in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma.
- Detailed Description
OBJECTIVES:
Primary
* To determine the overall survival of patients with newly diagnosed glioblastoma multiforme (GBM) with unmethylated MGMT promoter treated with bevacizumab and erlotinib hydrochloride after radiotherapy and temozolomide.
Secondary
* To determine the 12- and 24-month progression-free survival (PFS) of patients with newly diagnosed GBM with unmethylated MGMT promoter treated with this regimen.
* To assess radiographic response rates.
* To perform correlative tissue assays.
* To collect safety data on the combination of bevacizumab and erlotinib hydrochloride in patients with newly diagnosed GBM with unmethylated MGMT promoter treated with bevacizumab and erlotinib hydrochloride after radiotherapy and temozolomide.
OUTLINE: This is a multicenter study.
Patients undergo radiotherapy (either intensity-modulated radiation therapy or 3-D conformal radiotherapy) once daily 5 days a week and receive oral temozolomide concurrently with radiotherapy once daily for 6 weeks (as planned). Patients whose tumor has a methylated MGMT promoter are removed from study.
Approximately 4 weeks after completion of radiotherapy and temozolomide, patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment with bevacizumab and erlotinib hydrochloride repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at approximately 30 days and then every 3 months thereafter.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 115
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment erlotinib hydrochloride erlotinib and bevacizumab Treatment bevacizumab erlotinib and bevacizumab
- Primary Outcome Measures
Name Time Method Overall Survival From start of treatment, during treatment and every 3 months following the end of treatment until death. Median follow up at time of OS data was 33 months. Overall survival (OS) will be measured from the start of treatment until death from any cause. At data cut off patients remaining alive will be censored at the last known date of contact.
- Secondary Outcome Measures
Name Time Method Response Rate (RR) From the start of treatment, every 2 cycles (1 cycle = 28 days) during treatment until progressive disease Response Rate (RR) will be defined as the best response seen during treatment measured by CT/MRI scan every 8 weeks during treatment using McDonald Criteria.
CR=Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients off steroids.
PR=Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable/decreased dose of steroids.
Stable/No Response=Does not qualify for CR, PR, or progression. The designation of Stable/No Response requires a minimum of 8 weeks duration. Stable/decreased dose of steroids.
Progressive disease = 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease), worsening of evaluable disease, new lesions/site, failure to return for evaluation due to death or deteriorating condition.Progression Free Survival at 18 Months At 18 months from start of treatment Progression free survival (PFS) will be assessed by CT or MRI scan using McDonald criteria. Progressive disease (PD) is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Stable or increased dose of steroids. PFS will be measured from the start of treatment until first documentation of PD or death.
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population From the start of treatment, at the beginning of every cycle (1 cycle = 28 days) during treatment until 30 days after completion of treatment for up to 49 cycles. Toxicity data for combination treatment of erlotinib and bevacizumab will be collected on day 1 of every cycle (1 cycle = 28 days) during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following:
Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AEProgression-free Survival at 12 Months At 12 months from start of treatment Progression free survival (PFS) will be assessed by CT or MRI scan using McDonald criteria. Progressive disease (PD) is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Stable or increased dose of steroids. PFS will be measured from the start of treatment until first documentation of PD or death.
Trial Locations
- Locations (9)
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Neuro-Oncology Associates at Baylor University Medical Center, Dallas
🇺🇸Dallas, Texas, United States
Northwestern University, Northwestern Medical Faculty Foundation
🇺🇸Chicago, Illinois, United States
Evanston Hospital
🇺🇸Evanston, Illinois, United States
M.D. Anderson Cancer Center at University of Texas
🇺🇸Houston, Texas, United States
The Methodist Hospital Neurological Institute
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
🇺🇸Seattle, Washington, United States
M.D. Anderson Cancer Center at Orlando
🇺🇸Orlando, Florida, United States
Hollings Cancer Center at Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States