This phase I trial is studying the side effects and best dose of arsenic trioxide when given together with disulfiram in treating patients with metastatic and progressive melanoma. Drugs used in chemotherapy, such as disulfiram and arsenic trioxide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PRIMARY OBJECTIVES: I. Evaluate the tolerability of disulfiram and arsenic trioxide administration as a therapeutic combination. (Phase IB) SECONDARY OBJECTIVES: l. Determine the response rate (complete and partial responses) and time to progression of previously treated patients with metastatic malignant melanoma when treated with disulfiram plus Arsenic Trioxide. (Phase II) OUTLINE: This is a dose-escalation study of arsenic trioxide. Patients receive disulfiram orally (PO) twice daily and arsenic trioxide intravenously (IV) over 1-2 hours on Monday through Friday, alternating two weeks on treatment followed by two weeks off treatment. Courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Given PO
Given IV
Chao Family Comprehensive Cancer Center, University of California, Irvine
Orange, California, United States
Dose Escalation: Identification of Maximum Tolerated Dose
The dose will be escalated or reduced until a tolerable dose is reached. Dose toleration is determined by the absence of any grade III/IV toxicities. Arsenic trioxide will be administered intravenously at a starting dose of 0.05 mg/kg daily, 5 days per week, for 2 weeks. The patients then have 2 weeks off, followed by two weeks of daily administration. If the initial dose is tolerated, the patient will be dose escalated for the second two weeks of drug administration to 0.10 mg/kg/day for two additional weeks, followed by two weeks off. If the first dose escalation is tolerated, then a second dose escalation will be attempted to 0.15 mg/kg/day, the current dose recommended for leukemia. The 0.15 mg/kg/day dose will be continued for two weeks on alternating with two weeks off as long as this is tolerated to a maximum of 60 doses. For patients developing grade III/IV toxicity at a given dose level, they will be dose reduced by one level and remain on that dose for the trial.
Time frame: Up to 6 years
Response rate (complete or partial response)
Will be calculated as percentage of the study population. Data will be summarized in tabular form for publication.
Time frame: Up to 6 years
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