Disulfiram, Copper Gluconate, and Liposomal Doxorubicin for the Treatment of Patients with Relapsed or Refractory Sarcomas

Inclusion Criteria

• Subjects must have histologically sarcoma in relapsed or refractory or intolerant of existing therapies known to provide clinical benefit
• Subjects must have measurable disease by RECIST criteria at study enrollment
• Subjects must be >= 18 years old (yo) at the time of enrollment
• Performance status of Karnofsky/Lansky >= 50%
• Absolute neutrophil count >= 1,000/mcL
• Platelet count >= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Serum creatinine =< 1.5 X institutional limit of normal
• Cardiac shortening fraction of >= 27% or Ejection fraction of >= 50% on echocardiogram
• Corrected QT interval (QTc) =< 480msec on electrocardiogram (EKG).
• Patients must have normal serum copper levels and serum ceruloplasmin > 17mg/dL
• Patient must be able to swallow pills or consume the contents of the DSF and Cu capsules sprinkled on food
• Patients must have the ability to understand and the willingness to sign a written informed consent document
• Patients must abstain from alcohol during study
• Prior treatment toxicities must have stabilized or resolved to =< Grade 1 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 except alopecia, neuropathy and hematologic criteria (must meet absolute neutrophil count, platelet count, total bilirubin, AST [SGOT], ALT [SGPT], serum creatinine, cardiac shortening fraction/ejection fraction, and QTc criteria above)
• Patients must agree to pre- and post-treatment core needle tumor biopsies. Biopsies will not be performed if deemed unsafe by interventional radiologists that will be performing the procedure and is not part of the study team to avoid bias. Fresh tissue is required for the analyses. Archived tissue unfortunately cannot be used
• Patient must abstain from sexual intercourse or used appropriate, highly-effective birth control measures

Exclusion Criteria

• Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
• Patient has a history of allergy or hypersensitivity to any of the study drugs, their pharmaceutical class or any of their excipients. The patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of Liposomal Doxorubicin Prescribing Information package inserts or on the Investigator’s Brochure for DSF/Cu
• Patient has a concomitant serious medical or psychiatric illness that, in the opinion of the investigator, could compromise the patient's safety or the study data integrity
• Patient is currently enrolled in any other clinical protocol or investigational trial involving administration of antineoplastic compounds for the treatment of their sarcoma
• Any gastrointestinal disorders that will interfere with absorption of medications
• Patient is unwilling or unable to comply with study procedures
• Know condition preventing safe administration of copper such as a copper allergy or Wilson’s Disease
• Men who score >8 and women who score >4 on Alcohol Use Disorders Identification Test (AUDIT) questionnaire
• Principal Investigator (PI) feels participation in this study would be harmful or of no benefit to the patient