Paclitaxel and Carboplatin or Temozolomide in Treating Patients With Stage IV Melanoma

Mayo Clinic

Status and phase: Terminated; Phase 2

Conditions: Melanoma (Skin)

Treatments: Drug: temozolomide; Drug: carboplatin; Drug: paclitaxel

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00568451

P30CA015083 (U.S. NIH Grant/Contract)

06-002547 (Other Identifier)

NCI-2010-01794 (Registry Identifier)

MC057F (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic melanoma

  • Stage IV disease
  • Progressive disease
  • No known standard therapy that is potentially curative or proven capable of extending life expectancy exists

• Planning to undergo chemotherapy with paclitaxel and carboplatin OR temozolomide alone for progressive disease

• Measurable disease as defined by RECIST criteria

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy ≥ 3 months

• ANC ≥ 1,500/mL

• Platelet count ≥ 100,000/mL

• Hemoglobin ≥ 9 g/dL

• Creatinine ≤ 2.5 x upper limit of normal (ULN)

• AST ≤ 3 x ULN

• Alkaline phosphatase ≤ 3.0 x ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 1 month after completion of study therapy

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Active infection
  • NYHA class III or IV congestive heart failure

• No history of other malignancy within the past 5 years except for basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the cervix

• Willing to provide research blood samples

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from prior therapy

• At least 4 weeks since prior radiotherapy

• At least 4 weeks since prior chemotherapy (patients who received chemotherapy in the metastatic setting)

  • No prior chemotherapy treatment with agents similar to study drugs

• No prior chemotherapy in the metastatic setting (for chemo-naive patients)

• No concurrent enrollment in a different clinical study in which investigational procedures or agents are being used

• No other concurrent investigational agents

• No other concurrent chemotherapy or radiotherapy, including palliative radiotherapy

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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12 participants in 4 patient groups

PC (previously treated)

Experimental group

Description:

Previously chemotherapy treated cohorts: Paclitaxel and Carboplatin (PC)

Treatment:

Drug: paclitaxel

Drug: carboplatin

PC (chemo naive)

Experimental group

Description:

Chemotherapy-naive cohorts: Paclitaxel and Carboplatin (PC)

Treatment:

Drug: paclitaxel

Drug: carboplatin

TMZ (previously treated)

Experimental group

Description:

Previously chemotherapy treated cohorts: Temozolomide (TMZ)

Treatment:

Drug: temozolomide

TMZ (chemo naive)

Experimental group

Description:

Chemotherapy-naive cohorts: Temozolomide (TMZ)

Treatment:

Drug: temozolomide