Erlotinib and Bevacizumab in Treating Patients With Stage IV Melanoma
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving erlotinib together with bevacizumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving erlotinib together with bevacizumab works in treating patients with stage IV melanoma.
|Melanoma||Biological: bevacizumab Drug: erlotinib hydrochloride Genetic: fluorescence in situ hybridization Genetic: gene expression analysis Other: immunologic technique Other: laboratory biomarker analysis Procedure: biopsy||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Tarceva (Erlotinib) and Avastin (Bevacizumab) in the Treatment of Patients With Metastatic Melanoma|
- Number of Patients With Response [ Time Frame: At 6 months ]Per Response Evaluation Criteria in Solid Tumor (RECIST): Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
- Time to Disease Progression. [ Time Frame: up to one year after off-study date ]Time from on study date to date of progression in months, if the progression happened in the patient. Disease progression is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions with reference to the smallest sum LD since treatment began or the appearance of one or more new lesions.
- Progression-free Survival at 6 Months [ Time Frame: 6 months ]Patients with Progression-free survival at 6 months
- Number of Patients With Each Worst-grade Toxicity Response [ Time Frame: Day 1 of each 28-day cycle for 6 cycles (168 days) ]Number of patients with worst-grade toxicity at each of five grades following National Cancer Institute Common Toxicity Criteria with grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening/disabling, 5 = death.
|Study Start Date:||September 2004|
|Study Completion Date:||September 2008|
|Primary Completion Date:||August 2008 (Final data collection date for primary outcome measure)|
Experimental: Therapeutic Intervention
Tarceva and Avastin:
10mg/kg, slow IV infusion, Days 1 and 14
Other Name: AvastinDrug: erlotinib hydrochloride
150mg PO qd
Other Name: TarcevaGenetic: fluorescence in situ hybridization
Targeting multiple genetic aberrations in isolated tumor cells.Genetic: gene expression analysis
gene expression analysisOther: immunologic technique
immunologic techniqueOther: laboratory biomarker analysis
laboratory biomarker analysisProcedure: biopsy
- Determine the overall response rate, response duration, and frequency of progression-free survival at 6 months in patients with stage IV melanoma treated with erlotinib hydrochloride and bevacizumab.
- Determine objective responses in patients treated with this regimen.
- Determine the overall safety and tolerability of this regimen in these patients.
- Evaluate tissue blocks for EGFR by monoclonal antibody H11 (DAKO) or fluorescence in situ hybridization(FISH)7p12-specific probe-overexpression or amplification in patients treated with this regimen.
OUTLINE: This is a multicenter study.
Patients receive oral erlotinib hydrochloride once daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo tissue collection to analyze EGFR by monoclonal antibody H11 (DAKO) or fluorescence in situ hybridization (FISH) 7p12-specific probe-overexpression or amplification. Biological markers AKT, MAPK, p27, p21, CD13, CD34, and factor VIII are also measured.
After completion of study treatment, patients are followed periodically.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00466687
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center - Cool Springs|
|Nashville, Tennessee, United States, 37067-1631|
|Vanderbilt-Ingram Cancer Center at Franklin|
|Nashville, Tennessee, United States, 37067|
|Sarah Cannon Research Institute|
|Nashville, Tennessee, United States, 37203|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232-6838|
|Principal Investigator:||Jeffrey A. Sosman, MD||Vanderbilt-Ingram Cancer Center|