Carboplatin and ABI-007 in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery

OBJECTIVES:

Primary

- Assess the safety and antitumor activity of carboplatin and paclitaxel
albumin-stabilized nanoparticle formulation (ABI-007) in patients with unresectable
stage IV melanoma who have not received prior chemotherapy for their metastatic disease.
(Cohort 1)

- Assess the safety and antitumor activity of this regimen in patients with unresectable
stage IV melanoma who have received prior chemotherapy for their metastatic disease.
(Cohort 2)

Secondary

- Describe the impact of this regimen on parameters of immune function and angiogenesis in
these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy
for metastatic disease (yes vs no).

Patients receive paclitaxel albumin-stabilized nanoparticle formulation (ABI-007) IV over 30
minutes followed by carboplatin IV over 30 minutes on days 1, 8, and 15. Treatment repeats
every 28 days for at least 8 courses in the absence of disease progression or unacceptable
toxicity.

Blood and tumor tissue samples are collected periodically to evaluate secreted protein acidic
and rich in cysteine (SPARC) content of tumor tissue by immunohistochemistry and to explore
the impact of therapy on immune homeostasis. Samples are also analyzed by immunoenzyme
techniques for angiogenesis markers.

After completion of study treatment, patients are followed periodically for up to 2 years.

PROJECTED ACCRUAL: A total of 74 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed unresectable stage IV melanoma

- Measurable disease

- Must have formalin-fixed, paraffin-embedded tumor tissue available for secreted
protein acidic and rich in cysteine (SPARC) analysis pre-treatment (Mayo Clinic
patients must be willing to submit a repeat biopsy at time of tumor progression)

- Brain metastases allowed provided they were previously treated with no progression for
≥ 3 months

- Patients with known brain metastases may receive concurrent steroid treatment

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy ≥ 3 months

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL (may be transfused to meet this requirement)

- Creatinine ≤ 1.5 times upper limit of normal (ULN)

- Total bilirubin ≤ 1.5 times ULN (elevated bilirubin allowed in patients with
documented Gilbert's syndrome)

- AST ≤ 2.5 times ULN

- Alkaline phosphatase ≤ 2.5 times 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, the following:

- Active infection

- Congestive heart failure (New York Heart Association class III-IV heart disease)

- No peripheral neuropathy ≥ grade 2

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

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from prior therapy

- At least 4 weeks since prior radiotherapy

- At least 4 weeks since prior interferon or interleukin-2

- At least 4 weeks since prior chemotherapy (cohort 1 )

- No prior chemotherapy in the metastatic setting (cohort 2)

- No prior treatment for melanoma with any of the following agents:

- Platinum chemotherapy (e.g., carboplatin or cisplatin)

- Taxanes (e.g., paclitaxel or docetaxel)

- Paclitaxel albumin-stabilized nanoparticle formulation (ABI-007)

- No other concurrent chemotherapy

- No other concurrent investigational agents

- No concurrent radiotherapy, including palliative radiotherapy