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

This is an interventional treatment trial for Metastatic Pancreatic Adenocarcinoma Read More

Inclusion Criteria:

• Cohort 1 (dose escalation): histologic or cytologic proof of any solid tumor that is incurable with no standard therapy that is likely to make a major impact on clinical outcomes
• Cohort 2 (MTD) only: metastatic adenocarcinoma of the pancreas; prior systemic treatment for metastatic disease is allowed
• Cohort 2 (MTD) only: Patient is thought to be a short- or long-term candidate for chemotherapy in the opinion of the treating oncologist
• Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 7 days prior to registration)
• Platelet >= 100,000/ mm^3 (obtained =< 7 days prior to registration)
• Total bilirubin =< 2 x upper limit of normal (ULN) (obtained =< 7 days prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x ULN (obtained =< 7 days prior to registration)
• Creatinine =< 1.5 x ULN (obtained =< 7 days prior to registration)
• Hemoglobin >= 9.0 g/dL (obtained =< 7 days prior to registration)
• Cohort 2 (MTD) only: prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x ULN (only if muscle biopsy has not been waived, does not apply to non-Mayo sites that will not be conducting biopsies) (obtained =< 7 days prior to registration)
• Ability to provide written informed consent
• Life expectancy >= 12 weeks
• Cohort 2 (MTD) only: patient willing to undergo muscle biopsies at baseline and after 28 to 35 days of disulfiram/chemotherapy as required by the protocol unless the muscle biopsy has been waived after discussion with the principal investigator (PI); muscle biopsies will not be required at non-Mayo Clinic sites
• Cohort 2 (MTD) only: patient willing to have paraffin-embedded slides of the primary pancreas tumor or metastatic site, if available, sent to Mayo investigators for this study
• For women of childbearing potential only: negative urine or serum pregnancy test done =< 7 days prior to registration
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Able to swallow or have medication administered through a gastrostomy tube (G-tube) and absorb the medication
• Patient willing to complete a medication diary

• Patient agrees to use acceptable form of contraception during the study and for up to 30 days after last study drug dose if female partner is of childbearing potential

  • Acceptable forms of contraception:

    • Latex condom (always used with spermicide)
    • Diaphragm (always used with spermicide)
    • Cervical cap (always used with spermicide)

  • Acceptable forms of secondary contraception, when used along with a barrier method:

    • Hormonal contraception methods, including pills, patches, rings, or injections except progestin-only containing pills (i.e. "Mini-pill")
    • Tubal ligation
    • Partner's vasectomy
    • Intrauterine device (non-progesterone T)
    • Vaginal sponge (containing spermicide)

  • Other acceptable forms:

    • 100% commitment to abstinence

  • Unacceptable forms of contraception for women of childbearing potential:

    • Oral contraception containing progestins only
    • Intrauterine device (IUD) progesterone T
    • Female condom
    • Natural family planning (rhythm method) or breastfeeding
    • Fertility awareness
    • Withdrawal
    • Cervical shield

Exclusion Criteria:

• Known standard therapy for the patient's disease that is potentially curative
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, including localized infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements
• Untreated brain metastases

• Any of the following:

  • Pregnant women
  • Nursing women This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
• Other concurrent chemotherapy, immunotherapy, radiotherapy, any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) or receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Baseline of grade 2 or worse peripheral sensory neuropathy
• Receiving phenytoin
• Unable to abstain from alcohol for the duration of the study