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

NCT05210374 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE1720
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Relapsed Sarcomas

Keywords

Sarcoma,; osteosarcoma; rhabdomyosarcoma; Ewing sarcoma

Outcome Measures

Primary Outcomes (5)

• 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

  up to 30 days after last treatment

• Recommended phase 2 dose (RP2D) of DSF/Cu in combination with liposomal doxorubicin

  RP2D of DSF/Cu in combination with liposomal doxorubicin

  at end of cycle 1 (day 28)

• 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

  up to 30 days after last treatment

• Number of dose-limiting toxicities (DLT)

  Tolerability, as total number of defined as number of DLTs

  up to 30 days after last treatment

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

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

  up to 30 days after last treatment

Secondary Outcomes (18)

• Percent of participants with tumor response evaluated using RECIST v1.1

  At 2 months

• Median Overall Survival (OS)

  up to 30 days after last treatment

• Median Event free survival

  up to 30 days after last treatment

• Pharmacokinetics of DSF/Cu in combination with liposomal doxorubicin [Peak concentration (Cmax)]

  At hour 0 of Day 1 of lead-in week

• Pharmacokinetics of DSF/Cu in combination with liposomal doxorubicin [Peak concentration (Cmax)]

  At hour 2 of Day 1 of lead-in week

Study Arms (1)

DSF/Cu

EXPERIMENTAL

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

Drug: Disulfiram; Drug: Copper Gluconate; Drug: Liposomal Doxorubicin (Doxil)

Interventions

Disulfiram 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

DSF/Cu

Copper Gluconate 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

DSF/Cu

Liposomal Doxorubicin (Doxil) DRUG

To be given IV, 30mg/m2/dose To be administered day 1 of cycles Cycle length: 28 days, maximum 12 cycles

Also known as: Pegylated Liposomal Doxorubicin (PLD), Doxorubicin HCl Liposome Injection, Dox-SL

DSF/Cu

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44122, United States

RECRUITING

MeSH Terms

Conditions

Sarcoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma, Ewing

Interventions

Disulfiram; Gluconates; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Myosarcoma; Neoplasms, Muscle Tissue

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds; Sugar Acids; Hydroxy Acids; Carbohydrates

Study Officials

• Matteo Trucco, MD

  Cleveland Clinic, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matteo Trucco, MD

CONTACT

+1 216-444-8950; truccom@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2022
• First Posted: January 27, 2022
• Study Start: March 9, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Immediately following publication and for 3 years following publication
• Access Criteria: Researchers who provide a sound rationale for access

Locations

US (1)