Disulfiram in Patients With Metastatic Melanoma
Condition: Stage IV Melanoma
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Melanoma remains a malignancy that is largely resistant to chemotherapy. Metastatic disease
      responds poorly to the treatments used today with only 2 out of 30 drugs tested, DTIC and
      nitrosoureas, showing response rates greater than 10%, and complete responses are rare.
      DTIC-based regimen has been recognized as a standard chemotherapy for advanced melanoma, and
      temozolomide demonstrated efficacy equal to that of DTIC and is an oral alternative agent
      that also crosses the blood brain barrier. Randomized phase III trials have shown no survival
      benefit of adding other agents (cisplatin, BCNU, and tamoxifen). Biochemotherapy is being
      developed extensively with moderate improvement in the responsive rate (approximately 50%)
      and is under evaluation in randomized trial to identify whether there is survival benefit to
      this strategy, compared with chemotherapy alone. Recently, a randomized phase III study
      comparing chemotherapy (cisplatin, dacarbazine, and tamoxifen) with biochemotherapy (the same
      chemotherapy regimen plus high-dose IL-2 and interferon alfa) have shown 44% response rate
      for biochemotherapy vs. 27% for chemotherapy. However, the tendency toward an increased
      response rate in patients who received biochemotherapy did not translate into an increase in
      overall survival, and there was, in fact, a trend for a survival advantage in patients
      receiving chemotherapy alone (median survival: 10.7 vs 15.8 months). New agents (or
      combinations) need to be developed for this refractory malignancy.

      The purpose of this study is to determine the response rate and evaluate the toxicity of
      disulfiram (DSF) in the treatment of Stage IV melanoma.

      The advantages of using DSF in this phase I/II trial are the following:

        -  DSF has been used as a drug for many years for the treatment of alcoholism. Its
           mechanism, pharmacokinetics, toxicity/tolerable dose are well known, and this drug is
           relatively non-toxic by itself at therapeutic dose. Doses of greater than 3000mg/m2 can
           cause reversible confusion.

        -  DSF can be taken orally; therefore, it is convenient to administer.

        -  DSF can penetrate the blood-brain barrier (unlike dacarbazine and many other
           chemotherapy agents); therefore, it might have an active effect on CNS metastasis.

      This study is designed to include women and minorities, but is not designed to measure
      differences of intervention effect.
    


Intervention name(s): Disulfiram (DSF)
Intervention type(s): Drug
Intervention description(s): DSF pills at 250 mg will be given orally, two times a day. If this dose is tolerated, the dose will be escalated until the maximum tolerated dose is reached. Treatment will continue every day for 3 months or longer unless the disease gets worse, the side effects are too dangerous for the subject, or the subject decides to discontinue treatment.
Other intervention name(s): bis(diethylthiocarbamoyl) disulfide
Intervention MeSH terms: Disulfiram
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment