Clinical trial NCT00568451
Conditions: Melanoma (Skin)
Keywords: stage IV melanoma recurrent melanoma
Sponsor: Mayo Clinic
Start date: 2006-06-01; Completion date: 2012-04-01
Enrollment: 12 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: Previously chemotherapy treated cohorts: Paclitaxel and Carboplatin (PC) arm 2: Chemotherapy-naive cohorts: Paclitaxel and Carboplatin (PC) arm 3: Previously chemotherapy treated cohorts: Temozolomide (TMZ) arm 4: Chemotherapy-naive cohorts: Temozolomide (TMZ)
Interventions: intervention 1: carboplatin intervention 2: paclitaxel intervention 3: temozolomide
Intervention descriptions: intervention 1: AUC=2 intravenously on days 1, 8 and 15. Re-treat every 4 weeks until progression, unacceptable toxicity, or refusal intervention 2: 100mg/m\^2 intravenously on days 1, 8 and 15. Re-treat every 4 weeks until progression, unacceptable toxicity, or refusal intervention 3: 150mg/m\^2 at cycle 1, 200mg/m\^2 at cycle 2 and beyond, orally on days 1-5. Re-treat every 4 weeks until progression, unacceptable toxicity, or refusal. One treatment cycle=four weeks

Protocol documents: