Disulfiram and Chemotherapy in Treating Patients With Refractory Solid Tumors or Metastatic Pancreatic Cancer

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PRIMARY OBJECTIVE: I. To determine the maximally tolerated dose (MTD) of the combination of disulfiram and gemcitabine (gemcitabine hydrochloride) in unresectable solid tumor cancer patients (Cohort 1). SECONDARY OBJECTIVES: I. To describe the adverse event profile associated with this combination o...

PRIMARY OBJECTIVE: I. To determine the maximally tolerated dose (MTD) of the combination of disulfiram and gemcitabine (gemcitabine hydrochloride) in unresectable solid tumor cancer patients (Cohort 1). SECONDARY OBJECTIVES: I. To describe the adverse event profile associated with this combination of disulfiram and chemotherapy (Cohort 2). II. To describe changes in muscle area at the L3 level from baseline to 28 to 60 days from the baseline computed tomography (CT) scan in patients treated with disulfiram/chemotherapy and with placebo/chemotherapy (Cohort 2). III. To describe changes in fist-grip strength from baseline to 28 to 35 days of treatment with disulfiram/gemcitabine and with placebo/chemotherapy (Cohort 2). IV. To describe overall survival of pancreas cancer patients who disulfiram/chemotherapy or placebo/chemotherapy (Cohort 2). V. To estimate the response rate per Response Evaluation Criteria in Solid Tumors (RECIST) criteria around 1 month post-treatment in patients who receive disulfiram/chemotherapy and placebo/chemotherapy (Cohort 2). CORRELATIVE OBJECTIVE: I. To assess the effect of disulfiram and chemotherapy on the ubiquitin proteasome and autophagy pathways within muscle, as assessed by means of muscle biopsies performed at baseline and after 28 to 35 days of treatment (Cohort 2) (this is for Mayo only patients and can be waived upon permission from the principal investigator [PI]). OUTLINE: This is a phase I, dose-escalation study of disulfiram. COHORT I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15 and disulfiram orally (PO) on days 1-28 or days 1-35. COHORT II: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive chemotherapy at the discretion of the treating oncologist and disulfiram PO on days 1-28 or days 1-35. ARM II: Patients receive chemotherapy at the discretion of the treating oncologist and placebo PO on days 1-28 or days 1-35. After completion of study treatment, patients are followed up at 30 days, and then every 6 months for 3 years.

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