Paclitaxel and Carboplatin or Temozolomide in Treating Patients With Stage IV Melanoma
- Conditions
- Melanoma (Skin)
- Interventions
- Registration Number
- NCT00568451
- Lead Sponsor
- Mayo Clinic
- Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving paclitaxel together with carboplatin is more effective than giving temozolomide alone in treating patients with melanoma.
PURPOSE: This phase II trial is studying the side effects and how well giving paclitaxel together with carboplatin or giving temozolomide alone works in treating patients with stage IV melanoma.
- Detailed Description
OBJECTIVES:
* To assess the anti-tumor activity and toxicity profile of timed delivery of conventional paclitaxel and carboplatin (PC) in patients with stage IV melanoma who have received prior chemotherapy for their metastatic disease.
* To assess the anti-tumor activity and toxicity profile of timed delivery of conventional temozolomide (TMZ) chemotherapy in patients with stage IV melanoma who have received prior chemotherapy for their metastatic disease.
* To assess the anti-tumor activity and toxicity profile of timed delivery of conventional PC in patients with stage IV melanoma who have not received prior chemotherapy for their metastatic disease.
* To assess the anti-tumor activity and toxicity profile of timed delivery of conventional TMZ chemotherapy in patients with stage IV melanoma who have not received prior chemotherapy for their metastatic disease.
* To evaluate the changes of T-regulator cells, melanoma-specific functional parameters as a function of time in all four patient cohorts.
OUTLINE: Patients are stratified according to prior chemotherapy for metastatic disease (yes vs no) and scheduled chemotherapy regimen (paclitaxel and carboplatin vs temozolomide).
Beginning at the predicted day of C-reactive peptide (CRP) peak levels, patients receive paclitaxel IV and carboplatin IV on days 1, 8, and 15 OR oral temozolomide alone on days 1-5. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection periodically for pharmacological studies. Samples are analyzed for CRP quantification via ELISA; presence and number of circulating blood T-regulator cells via immunophenotyping for CD4/CD25+ and CD4/fox-p3+ T cells; level of functional immunity against melanoma specific antigens (MART-1, tyrosinase, and gp100) and survivin in patients that are HLA-A2+ via intracellular staining; total number of cytotoxic T lymphocytes (CTLs) capable of reacting against melanoma targets via tetramer staining (Becton-Coulter); and quantification of interferon γ-producing, peptide-specific CTLs via multicolor conventional flow cytometry.
After completion of study treatment, patients are followed every 3 months for up to 2 years.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 12
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PC (previously treated) carboplatin Previously chemotherapy treated cohorts: Paclitaxel and Carboplatin (PC) PC (previously treated) paclitaxel Previously chemotherapy treated cohorts: Paclitaxel and Carboplatin (PC) PC (chemo naive) carboplatin Chemotherapy-naive cohorts: Paclitaxel and Carboplatin (PC) TMZ (previously treated) temozolomide Previously chemotherapy treated cohorts: Temozolomide (TMZ) PC (chemo naive) paclitaxel Chemotherapy-naive cohorts: Paclitaxel and Carboplatin (PC) TMZ (chemo naive) temozolomide Chemotherapy-naive cohorts: Temozolomide (TMZ)
- Primary Outcome Measures
Name Time Method Number of Participants With an Objective Tumor Status of Either a Complete Response(CR) or Partial Response (PR), According to RECIST (Response Evaluation Criteria in Solid Tumors) Criteria Every other cycle of therapy (cycle=4 weeks) for the first 6 cycles of treatment Response that was noted on 2 consecutive evaluations for at least 4 weeks apart.
CR: Disappearance of all target lesions; PR: At least a 30 percent of decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Target lesions: All measurable lesions up to a maximum of 10 lesions representative of all involved organs.
- Secondary Outcome Measures
Name Time Method Time to Disease Progression up to 2 years Time to disease progression was defined as the time from registration to documentation of disease progression. Disease progression was measured according to the RECIST criteria. Progression: At least a 20 percent increase in the sum of of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Survival Time up to 2 years Survival time was defined as the time from registration to death due to any cause.
Duration of Response for All Evaluable Patients Who Have Achieved an Objective Response up to 2 years Duration of response was defined as the date at which the participant's objective status was first noted to be either a Complete Response or Partial Response to the date the progression was documented.
Number of Participants Who Experienced Changes in Immunologic Profile (CD4/CD25+ Cells, CD4/Fox-p3+ T Cells) Within a Treatment up to 2 years Time series plot of the number of circulating cells will be constructed. The resulting plots will be visually inspected for trends within and between treatments. For each cell type, a point and an interval estimate of the number of participants (receiving a given treatment) who had at least a 2-fold increase in the number of circulating cells of that type will be constructed using the properties of the binomial distribution.
Number of Participants Who Experienced Changes in Immunologic Profile (MART-1, Tyrosinase, and gp100) Within a Treatment up to 2 years For those patients who are HLA-A2+, the maximum post-treatment levels of MART-1, tyrosinase, and gp100 will be determined. For each of these specific melanoma specific antigens, the number of participants (within a given treatment) who gained or maintained immunity based on the maximum post-treatment level of that specific melanoma specific antigen will be determined.
Number of Participants Who Experienced Changes in Immunologic Profile (IFNγ Producing Peptide Specific CTLs) Within a Treatment up to 2 years For each patient, a time series plot of the number of IFNγ producing peptide specific CTLs will be constructed. The resulting plots will be visually inspected for trends within and between treatments. A point and an interval estimate of the number of participants (receiving a given treatment) who had at least a 2-fold increase in the number of the number of IFNγ producing peptide specific CTLs will be constructed using the properties of the binomial distribution.
Trial Locations
- Locations (1)
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States