The purpose of this study is to test the safety of combining the disulfiram (DSF) and copper gluconate (Cu) to liposomal doxorubicin to treat patients with sarcomas that recurred or did not respond to initial treatment.
Must have histologically confirmed relapsed or refractory sarcoma.
Must have measurable disease by RECIST criteria at study enrollment
Performance status of Karnofsky/Lansky ≥50%
Absolute neutrophil count ≥1,000/mcL
Has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
Has a history of allergy or hypersensitivity to any of the study drugs, their pharmaceutical class or any of their excipients. The participant 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.
Has a concomitant serious medical or psychiatric illness that, in the opinion of the investigator, could compromise the participant's safety or the study data integrity.
Is currently enrolled in any other clinical protocol or investigational trial involving administration of antineoplastic compounds for the treatment of their sarcoma.
Single group
Disulfiram
DrugTo be taken orally (PO) daily in the AM, rounded for pill size (max 480mg/day). To be administered day 1-7 of lead-in week and day 1-28 cycles Cycle length: 28 days, maximum 12 cycles Level -1 (150mg/m\^2/day) Level 0 (225mg/m\^2/day) Level 1 (300mg/m\^2/day), max 480mg/day
Copper Gluconate
DrugTo be taken orally (PO), 5.2mg/m2/day daily in the PM, rounded for pill size (max 9mg/day) To be administered day 1-7 Lead-in week and day 1-28 cycles Cycle length: 28 days, maximum 12 cycles
Liposomal Doxorubicin (Doxil)
DrugTo be given IV, 30mg/m2/dose To be administered day 1 of cycles Cycle length: 28 days, maximum 12 cycles
Safety as measured by percent of participants experiencing grade 3+ with at least possible attribution to study drug using CTCAE 5.0 guidelines
Safety as measured by percent of participants experiencing grade 3+ with at least possible attribution to study drug using CTCAE 5.0 guidelines
Recommended phase 2 dose (RP2D) of DSF/Cu in combination with liposomal doxorubicin
RP2D of DSF/Cu in combination with liposomal doxorubicin
Number of participants able to take at least 80% of the drug doses during the first cycle of treatment
Feasibility: Number of participants able to take at least 80% of the drug doses during the first cycle of treatment, assessed by the medication diary patients will be asked to keep
Number of dose-limiting toxicities (DLT)
Tolerability, as total number of defined as number of DLTs
Percent of participants with tumor response evaluated using RECIST v1.1
Tumor response will be evaluated per RECIST v1.1 criteria - percent of participants with complete response, partial response, stable disease and progressive disease reported
Median Overall Survival (OS)
Median OS defined as the time from participant enrollment on study to time of death
Median Event free survival
Median Event free survival defined as the time from participant enrollment on study to time of disease progression (PD) per RECIST v1.1,. PD defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Pharmacokinetics of DSF/Cu in combination with liposomal doxorubicin [Peak concentration (Cmax)]
Pharmacokinetics of DSF/Cu in combination with liposomal doxorubicinbased on samples collected - Peak concentration (Cmax)
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