Back to results

Disulfiram With Copper Gluconate and Liposomal Doxorubicin in Treatment-Refractory Sarcomas

Primary Purpose

Relapsed Sarcomas

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Disulfiram

Copper Gluconate

Liposomal Doxorubicin (Doxil)

About this trial

This is an interventional treatment trial for Relapsed Sarcomas focused on measuring Sarcoma,, osteosarcoma, rhabdomyosarcoma, Ewing sarcoma

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Must have histologically confirmed relapsed or refractory sarcoma.
Must have measurable disease by RECIST criteria at study enrollment
Performance status of Karnofsky/Lansky ≥50%
Must have normal organ and marrow function as defined below:
- Absolute neutrophil count ≥1,000/mcL
- Platelet count ≥ 100,000/mcL
- Total bilirubin within normal institutional limits
- AST (SGOT) ≤ 2.5 X institutional upper limit of normal
- ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
- Serum Creatinine ≤1.5X institutional limit of normal
Must be able to swallow pills or consume the contents of the DSF and Capsules sprinkled on food.
Participants, or parent/guardians for participants <18 years old (yo), must have the ability to understand and the willingness to sign a written informed consent document.
Must abstain from alcohol during study.
Prior treatment toxicities must have stabilized or resolved to ≤ Grade 1 according to NCI CTCAE Version 5.0 except alopecia, neuropathy and hematologic criteria (must meet normal organ and marrow function criteria above).
Participants ≥18yo must agree to pre-and post-treatment core needle tumor biopsies. For participants <18yo biopsies are optional. 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.
Must abstain from sexual intercourse or used appropriate, highly-effective birth control measures.

Exclusion Criteria:

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.
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.
Investigator feels participation in this study would be harmful or of no benefit to the potential participant

Sites / Locations

Cleveland Clinic, Case Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DSF/Cu

Arm Description

A 3+3 dose escalation design will be used to determine the recommended phase 2 dose (RP2D) of DSF/Cu in combination with liposomal doxorubicin. There will be a 7 day "lead-in" week of Disulfiram (DSF)/Copper Gluconate (Cu). The disulfiram and the copper gluconate will be dosed once a day. Disulfiram in the morning and copper gluconate in the evening. Same total daily dose every 4 week (28 days) administration of liposomal doxorubicin (Doxil) 30mg/m2/dose IV Cycle length: 28 days Maximum 12 cycles

Outcomes

Primary Outcome Measures

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

Number of participants who experienced drug-attributed grade 3+ Adverse events per CTCAE5.0

Secondary Outcome Measures

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)