Carboplatin, Paclitaxel, and Temozolomide for Patients With Metastatic Melanoma

Over the past several decades, significant research has been conducted to try to identify
active chemotherapeutic agents for the treatment of melanoma. The rationale for combining
taxanes and platinum agents is that both have activity in melanoma; in vitro and clinical
data suggest synergy between these drugs when used in combination in a wide variety of
tumors, including melanoma; and the toxicity profiles of these agents do not overlap.
Temozolomide (a drug approved for the treatment of melanoma) has been combined with other
drugs, including taxanes and platinums, in previous clinical trials for melanoma.
Specifically, a previous phase I study of the combination of temozolomide, paclitaxel, and
carboplatin in melanoma showed objective responses. The efficacy of this combination is now
being studied in this phase II trial.

Inclusion Criteria:

- All patients with biopsy proven advanced melanoma are eligible if there is measurable
disease.

- Patients must have a life expectancy of at least 12 weeks.

- Prior surgery, immunotherapy, minimal chemotherapy (1 drug for less than 4 months), or
radiotherapy for primary tumor is acceptable but must be completed at least 4 weeks
from study entry, and patient should have completely recovered from such procedures.

- Patients must have a Zubrod performance status of 0-2.

- Patients must sign an informed consent.

- Patients should have adequate bone marrow function defined by an absolute peripheral
granulocyte count of ≥ 1500 cells/mm3, hemoglobin > 8 g/dl, platelet count ≥ 100
000/mm3.

- Patients should have a normal hepatic function with a total bilirubin < 1.5 the upper
limit of normal (ULN) and serum glutamic oxaloacetic transaminase (SGOT) or serum
glutamic-pyruvic transaminase (SGPT) < 2 times the upper limit of normal (ULN),and
adequate renal function as defined by a serum creatinine ≤ 1.5 times the ULN.

- Men and women of childbearing potential must be willing to consent to using effective
contraception while on treatment and at least for 3 months.

- Patients with brain metastases are eligible if they have been appropriately treated,
are asymptomatic

Exclusion Criteria:

- Pregnant women or nursing mothers are not eligible.

- Patients must not receive any other concurrent chemotherapy or radiation during this
trial.

- Patients with severe medical problems that would interfere with the therapy are not
eligible.