Neoplasms

All Conditions

Rare Diseases

Sarcoma

Osteosarcoma

Sarcoma, Ewing

Rhabdomyosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Ewing Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Alcohol Deterrents

Micronutrients

Anti-Infective Agents

Central Nervous System Depressants

Mineral

Doxorubicin

Liposomal doxorubicin

Disulfiram

Copper

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Trace Elements

Ethanol

Copper Supplement

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

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

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

Copper Gluconate

To be given IV, 30mg/m2/dose

To be administered day 1 of cycles

Cycle length: 28 days, maximum 12 cycles

Liposomal Doxorubicin (Doxil)

Matteo Trucco, MD

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.

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.

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

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

Safety as measured by percent of participants experiencing grade 3+ with at least possible attribution to study drug using CTCAE 5.0 guidelines

RP2D of DSF/Cu in combination with liposomal doxorubicin

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

Tolerability, as total number of defined as number of DLTs

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

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 OS defined as the time from participant enrollment on study to time of death

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 doxorubicinbased on samples collected - Peak concentration (Cmax)

Pharmacokinetics of DSF/Cu in combination with liposomal doxorubicinbased on samples collected - area under the concentration-vs-time curve (AUC)

Pharmacokinetics of DSF/Cu in combination with liposomal doxorubicinbased on samples collected - clearance and average steady state concentrations for disulfiram and its active metabolites, S-methyl N,N-dietylthiolcarbamate (DETC-ME) and bis-diethyldithiocarbamate-copper complex (CuET)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Disulfiram With Copper Gluconate and Liposomal Doxorubicin in Treatment-Refractory Sarcomas	NCT05210374	Relapsed Sarcom...	Disulfiram Copper Gluconat... Liposomal Doxor...	1 Year -	Case Comprehensive Cancer Center
Disulfiram With Copper Gluconate and Liposomal Doxorubicin in Treatment-Refractory Sarcomas	NCT05210374	Relapsed Sarcom...	Disulfiram Copper Gluconat... Liposomal Doxor...	1 Year -	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for sarcoma,

Every month we try and update this database with for sarcoma, cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for sarcoma,

Every month we try and update this database with for sarcoma, cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for sarcoma, cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.