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

NCT ID: NCT05210374

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-09
• Study Completion Date: 2026-12-31

Brief Summary

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.

Detailed Description

DSF blocks an enzyme called aldehyde dehydrogenase (ALDH). ALDH breaks down substances in the body that can be toxic. ALDH also appears to be important for making many cancers resistant to chemotherapy drugs like liposomal doxorubicin. The study team believes giving DSF with liposomal doxorubicin will help make the cancers sensitive to the liposomal doxorubicin, making it work better. Cu is an FDA approved dietary food supplement and has been shown in laboratory research to improve how DSF works, which is the rational for giving DSF with Cu. It is currently unknown if and at what dose DSF is safe to be given in this combination. Though DSF has been used for over 60 years for the treatment of alcoholism, this is the first time DSF/Cu is being tested in combination with liposomal doxorubicin in humans.

The primary objectives of this study are to:

Measure the feasibility, safety and tolerability of DSF/Cu in combination with liposomal doxorubicin

Secondary objectives of this study are to:

Measure tumor response, survival, and pharmacokinetics of the combination.

Conditions

Relapsed Sarcomas

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DSF/Cu

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

Group Type: EXPERIMENTAL

Disulfiram

Intervention Type: DRUG

To 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

Intervention Type: DRUG

To 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)

Intervention Type: DRUG

To be given IV, 30mg/m2/dose

To be administered day 1 of cycles

Cycle length: 28 days, maximum 12 cycles

Interventions

Disulfiram

To 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

Intervention Type: DRUG

Copper Gluconate

To 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

Intervention Type: DRUG

Liposomal Doxorubicin (Doxil)

To be given IV, 30mg/m2/dose

To be administered day 1 of cycles

Cycle length: 28 days, maximum 12 cycles

Intervention Type: DRUG

Other Intervention Names

Pegylated Liposomal Doxorubicin (PLD); Doxorubicin HCl Liposome Injection; Dox-SL

Eligibility Criteria

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

• Minimum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matteo Trucco, MD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic, Case Comprehensive Cancer Center

Locations

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Matteo Trucco, MD

Role: CONTACT

truccom@ccf.org

+1 216-444-8950

Facility Contacts

Matteo Trucco, MD

Role: primary

truccom@ccf.org

216-444-8950

Other Identifiers

CASE1720

Identifier Type: -

Identifier Source: org_study_id