Temozolomide and Everolimus 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. Everolimus may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Giving everolimus together with temozolomide may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving everolimus together with temozolomide works in treating patients with stage IV melanoma that cannot be removed by surgery
Genetic: reverse transcriptase-polymerase chain reaction
Other: flow cytometry
Other: immunohistochemistry staining method
Other: immunologic technique
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Temozolomide and Everolimus (RAD001) Therapy for Metastatic Melanoma|
- 9-week progression-free survival rate [ Designated as safety issue: No ]
- Survival time [ Designated as safety issue: No ]
- Time to disease progression [ Designated as safety issue: No ]
- Confirmed response rate (complete response and partial response) [ Designated as safety issue: No ]
- Microvascular density and VEGF expression as assessed by IHC [ Designated as safety issue: No ]
- Plasma VEGF levels at baseline, 9 weeks, and at progression [ Designated as safety issue: No ]
- Immunologic parameters [ Designated as safety issue: No ]
- MGMT (O-6-methylguanine-DNA methyltransferase) [ Designated as safety issue: No ]
|Study Start Date:||January 2008|
|Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
- Estimate the 9-week progression-free survival rate for patients with stage IV malignant melanoma treated with everolimus and temozolomide.
- Evaluate overall survival time.
- Evaluate time to disease progression.
- Assess the toxicity profile of the combination of everolimus and temozolomide in patients with stage IV malignant melanoma.
- Assess the clinical benefit rate (i.e., stable disease, partial remission, and complete response rates).
- Describe the impact of therapy on parameters of angiogenesis and immunity (systemic and tumor microenvironment).
OUTLINE: This is a multicenter study.
Patients receive oral everolimus once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and oral temozolomide once a day on days 8-12 for course 1 only. For course 2 and all subsequent courses, patients receive oral everolimus once a day on days 1-5, 8-12, 15-19, and 22-26 and oral temozolomide once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
All patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for relative numbers of T, B, and NK cells via flow cytometry, quantitative immunoglobulin levels (IgG, IgM, and IgA), Tetramer/ELISPOT CTL frequencies to CMV/EBV immunodominant antigens, V beta T cell spectratyping, and VEGF levels via ELISA.
After completion of study treatment, patients are followed every 8 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00521001
Show 198 Study Locations
|Study Chair:||Ravi D. Rao, MD, MBBS||Mayo Clinic|
|Investigator:||Svetomir Markovic, MD, PhD||Mayo Clinic|
|Investigator:||William J. Maples, MD||Mayo Clinic|
|Investigator:||Michael K. Gornet, MD||Mayo Clinic Hospital|
|Investigator:||Edward T. Creagan, MD||Mayo Clinic|
|Investigator:||Barbara A. Pockaj, MD||Mayo Clinic Hospital|
|Investigator:||Judith S. Kaur, MD||Mayo Clinic|