Temozolomide and Everolimus in Treating Patients With Stage IV Melanoma That Cannot be Removed by Surgery
Summary
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
Description
OBJECTIVES:
Primary
- Estimate the 9-week progression-free survival rate for patients with stage IV malignant melanoma treated with everolimus and temozolomide.
Secondary
- 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.
Study Design
Masking: Open Label, Primary Purpose: Treatment
Conditions
Melanoma (Skin)
Intervention
everolimus, temozolomide, reverse transcriptase-polymerase chain reaction, flow cytometry, immunohistochemistry staining method, immunologic technique
Location
Aurora Presbyterian Hospital
Aurora
Colorado
United States
80012
Status
Completed
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00521001
- Information obtained from ClinicalTrials.gov on July 12, 2012
Medical and Biotech [MESH] Definitions
Reverse Transcriptase Polymerase Chain Reaction
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Genes, Pol
DNA sequences that form the coding region for retroviral enzymes including reverse transcriptase, protease, and endonuclease/integrase. "pol" is short for polymerase, the enzyme class of reverse transcriptase.
Reverse Transcriptase Inhibitors
Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.
Gene Products, Pol
Retroviral proteins coded by the pol gene. They are usually synthesized as a protein precursor (POLYPROTEINS) and later cleaved into final products that include reverse transcriptase, endonuclease/integrase, and viral protease. Sometimes they are synthesized as a gag-pol fusion protein (FUSION PROTEINS, GAG-POL). pol is short for polymerase, the enzyme class of reverse transcriptase.
Taq Polymerase
A heat stable DNA-DIRECTED DNA POLYMERASE from the bacteria Thermus aquaticus. It is widely used for the amplification of genes through the process of POLYMERASE CHAIN REACTION. EC 2.7.7.-.
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