Ensayos clínicos

Inclusion Criteria:

• Adult males and females, age ≥ 18 years.
• 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.
• Laboratory values obtained ≤ 7 days prior to registration:
  • ANC ≥ 500/mm^3;
  • Platelet ≥ 100,000/mm^3;
  • Total bilirubin ≤ 2 x upper limit of normal (ULN);
  • AST (SGOT) ≤ 3 x ULN;
  • Creatinine ≥ 1.5 x ULN;
  • Hemoglobin ≥ 9.0 g/dL.
• Cohort 2 (MTD) only: PT/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).
• 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 or chemotherapy/placebo therapy as required by the protocol unless the muscle biopsy has been waived after discussion with the PI. Muscle biopsies will not be required/performed 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.
• ECOG performance status (PS) 0, 1 or 2.
• Able to swallow or have medication administered through a 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;
  • 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-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.