Temozolomide and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery
RATIONALE: 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. 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 temozolomide together with bevacizumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving temozolomide together with bevacizumab works in treating patients with stage IV melanoma that cannot be removed by surgery.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Temozolomide Combined With Bevacizumab in Metastatic Melanoma. A Multicenter Phase II Trial|
- Clinical benefit number of patients with complete response [CR], partial response [PR], or stable disease) according to RECIST criteria [ Time Frame: at 12 weeks ] [ Designated as safety issue: No ]
- Best overall response (CR, PR) according to RECIST criteria [ Time Frame: from trial treatment start until PD ] [ Designated as safety issue: No ]
- Duration of response [ Time Frame: time from disease stabilisation until PD ] [ Designated as safety issue: No ]
- Progression free survival [ Time Frame: time from trial registration until disease progression or death ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: time from trial registration until death ] [ Designated as safety issue: No ]
- Adverse events [ Time Frame: time from start trial treatment until 30 days after treatment stop. Adverse events will be assessed according to NCI CTCAE v3.0. ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2007|
|Study Completion Date:||October 2011|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Experimental: Combination Therapy Temozolomide & Bevacizumab
10 mg/kg i.v., on day 1 of every cycle (14 days) until PD or any other event qualifying for stopping treatment
Other Name: AvastinDrug: temozolomide
150 mg/m2 p.o., on days 1-7 of every cycle (14 days) until PD or any other event qualifying for stopping treatment
Other Name: Temodal
- To evaluate the efficacy of temozolomide in combination with bevacizumab in patients with unresectable stage IV melanoma.
- To evaluate the safety and tolerability of this regimen.
- To evaluate the prognostic and predictive significance of circulating endothelial cells and endothelial progenitor cells in patients treated with this regimen.
- To predict tumor response and outcome in patients treated with this regimen by measuring hypermethylation of the tumor.
OUTLINE: This is a multicenter study.
Patients receive oral temozolomide once daily on days 1-7 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Blood is collected at baseline and on day 1 of course 2. Samples are analyzed for circulating endothelial cells and endothelial progenitor cells by flow cytometry and pro- and anti-angiogenic serum factors by ELISA. Paraffin-embedded tumor tissue is analyzed for MGMT promoter methylation status by methylation-specific PCR; MGMT protein expression by IHC; and MSH2, MSH6, and MLH-1 expression (DNA repair enzymes).
After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 1 year.