Clinical trial NCT00568451: Paclitaxel and Carboplatin or Temozolomide in Treating Patients With Stage IV Melanoma
Official title: Releasing the Cancer Patient's Immune System From Down-regulation With Timed Delivery of Standard Chemotherapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Melanoma (Skin)
Keywords: stage IV melanoma
recurrent melanoma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-12-06
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: Every other cycle of therapy (cycle=4 weeks) for the first 6 cycles of treatment
Secondary outcomes:
measure: Time to Disease Progression
timeFrame: up to 2 years
measure: Survival Time
timeFrame: up to 2 years
measure: Duration of Response for All Evaluable Patients Who Have Achieved an Objective Response
timeFrame: up to 2 years
measure: Number of Participants Who Experienced Changes in Immunologic Profile (CD4/CD25+ Cells, CD4/Fox-p3+ T Cells) Within a Treatment
timeFrame: up to 2 years
measure: Number of Participants Who Experienced Changes in Immunologic Profile (MART-1, Tyrosinase, and gp100) Within a Treatment
timeFrame: up to 2 years
measure: Number of Participants Who Experienced Changes in Immunologic Profile (IFNγ Producing Peptide Specific CTLs) Within a Treatment
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Svetomir Markovic, MD, PhD
role: STUDY_CHAIR
References: