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)

Case Comprehensive Cancer Center

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Adenocarcinoma

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Hematinics

Liver Extracts

Subjects with neuroendocrine prostate cancer (NEPC)

Copper will be administered intravenously at a dose of 1, 3, 5, or 7 mg on cycle 1 days 1, 8, 15. Disulfiram will administered orally at a dose of 80 mg three times a day starting on cycle 1 day 2. Copper gluconate will be administered orally at a dose of 1.5 mg three times a day starting on cycle 1 day 16.

Subjects with adenocarcinoma CRPC with non-liver/peritoneal metastases (lymph nodes, bone, or lung)

Copper will be administered intravenously at a dose of 1, 3, 5, or 7 mg on cycle 1 days 1, 8, 15. Disulfiram will administered orally at a dose of 80 mg three times a day starting on cycle 1 day 2. Copper gluconate will be administered orally at a dose of 1.5 mg three times a day starting on cycle 1 day 16.

Subjects with adenocarcinoma CRPC with liver and/or peritoneal metastases

Copper will be administered intravenously at a dose of 1, 3, 5, or 7 mg on cycle 1 days 1, 8, 15. Disulfiram will administered orally at a dose of 80 mg three times a day starting on cycle 1 day 2. Copper gluconate will be administered orally at a dose of 1.5 mg three times a day starting on cycle 1 day 16.

1 mg, 3 mg, 5 mg or 7 mg intravenously on cycle 1 day 1, 8 and 15

80 mg three times a day

Source of disulfiram: Cantex Pharmaceuticals

1.5 mg three times a day

Source of copper gluconate: Cantex Pharmaceuticals

Copper gluconate

Daniel George, MD

The purpose of this study is to determine the safety and optimal dosing of intravenous copper chloride and disulfiram in men with metastatic castrate-resistant prostate cancer (CRPC). Eligible men will have neuroendocrine prostate cancer (NEPC), adenocarcinoma CRPC with non-liver/peritoneal metastases (lymph nodes, bone, or lung) or adenocarcinoma CRPC with liver and/or peritoneal metastases. Subjects will receive three doses of intravenous copper chloride and take disulfiram and oral copper gluconate until disease progression (up to two years). Subjects will also undergo a PET scan with radioactive copper 64 to measure the levels of copper in their tumor. The central hypotheses of this project are that (a) copper chloride and disulfiram are safe to give together and that (b) the combination of disulfiram with copper will have efficacy for both mCRPC and NEPC.

A Phase Ib Study of Intravenous Copper Loading With Oral Disulfiram in Metastatic, Castration Resistant Prostate Cancer

Safety (NCI CTC v4.0) and tolerability of IV CuCl2 and DSF in men with mCRPC

Radiographic PFS based on PCWG3 criteria or based on the onset of a skeletal related event. Imaging obtained every 12 weeks.

Give 1 For Dad Campaign

The V Foundation for Cancer Research

Peter Michael Foundation

Cantex Pharmaceuticals

Professor of Medicine

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

* DSF (dose level (DL) 1=125mg, DL 2=250mg, DL 3=375 mg, DL 4=500mg). DSF starts at DL 2 and escalated using the Time-to-Event Continual Reassessment Method
* 3 day lead-in of oral DSF once daily (QD) prior to surgery (optional)
* 2 mg Cu gluconate 3 times daily (TID) on days when DSF is given (optional pre-surgery)
* Surgery performed per routine clinical care.
* After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study).
* RT 4-6 weeks following surgery at 60 Gy in 30 daily fractions.
* TMZ from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care.
* DSF QD and Cu TID during chemoradiotherapy as per preoperative dose
* 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.

* Surgery performed per routine clinical care.
* RT 4-6 weeks following surgery at 60 Gy in 30 daily fractions.
* TMZ from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care.
* DSF QD and Cu TID during chemoradiotherapy as per preoperative dose
* 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
* If a patient develops recurrent tumor during follow-up and plans to undergo another resection, he/she may opt for an optional preoperative DSF study prior to salvage surgery.

Surgery

Radiation

Jiayi Huang, M.D.

The proposed phase I/II study of disulfiram (DSF) for patients with presumed glioblastoma multiforme (GBM) based on magnetic resonance imaging (MRI) or biopsy, including administration before surgery and during adjuvant chemoradiotherapy. Patients will be treated with 3 days of preoperative DSF/copper (Cu) prior to their surgery (or biopsy), which will be followed by collection of tumor samples during surgery for analysis of drug uptake. After the surgery, patients will receive standard radiation therapy (RT) and temozolomide (TMZ) with the addition of concurrent DSF/Cu.

Disulfiram/Copper With Concurrent Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

A Phase I/II Dose-escalation and Dose-expansion Study of Disulfiram/Copper With Concurrent Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

* The maximum tolerated dose (MTD) of DSF is defined as the dose level at which 20% of the cohort experience dose-limiting toxicity (DLT) within 18 weeks from start of RT (or 12 weeks from the end of RT if there is a delay in RT). MTD is assessed from the first dose of DSF in combination with TMZ and RT; patients will not be assessed for DLT during the pre-surgery period when they are receiving the lead-in doses of DSF.
* A DLT is defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications/TMZ which occurs within 18 weeks following the first dose of DSF with RT+TMZ (corresponding to approximately 6 weeks during RT and 12 weeks after RT)

The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

-The ratios of intratumor concentration of DSF metabolite (ditiocarb-copper complex) relative to their corresponding plasma concentration will be determined using mass spectrometer

-Proteasome activity of GBM tissue will be measured using fluorometric proteasome assay

-Amount of DNA breaks will be quantified using gamma-H2AX phosphorylation (pH2AX) assay

-≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids. The absolute increase in any dimension must be at least 5mm when calculating the products

* Significant increase in T2/FLAIR nonenhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy not caused by comorbid events
* Any new measureable lesion
* Clear clinical deterioration not attributable to other causes apart from the tumor (e.g. seizures, medication adverse effects, complications of therapy, cerebrovascular events, infection, and so on) or changes in corticosteroid dose
* Failure to return for evaluation as a result of death or deteriorating condition; or clear progression of nonmeasurable disease

-Pseudoprogression is defined as a transient increase of tumor after chemoradiotherapy that subsequently stabilizes without a change of therapy

Washington University School of Medicine

Disulfiram (DSF; oral) / copper gluconate (Cu; oral) dosed at 125 mg / 2 mg, twice daily. Temozolomide will be administered following the standard Stupp protocol at a dose of 75 mg/m2 for 42 days with concurrent radiation therapy. Temozolomide maintenance dose will be 150 mg/m2 once daily on Days 1-5 of every 28-day cycle while DSF-Cu is continued twice daily, as tolerated, for the duration of the Temozolomide adjuvant treatment. Patients demonstrating continued benefit from the adjuvant temozolomide after 6 cycles can continue treatment to a maximum of 12 cycles

Copper gluconate is taken orally, twice daily

Asadullah Khan, MD

One of Disulfiram antitumor effects suggested in preclinical studies is MGMT (methyl-guanine-methyl-transferase) inhibition. Disulfiram MGMT inhibitory effect is enhanced by addition of Copper. This study evaluates the impact of Disulfiram (DSF) + Copper (Cu) combination when added to standard Temozolomide in the treatment of unmethylated Glioblastoma Multiforme (GBM) patients.

Glioblastoma is the most common malignant primary brain tumor and one of the most devastating cancers. The current standard of care for glioblastoma includes maximal safe resection followed by radiotherapy and temozolomide, which results in a median progression-free survival of less than 7 months, and median overall survival (OS) of less than 15 months. Moreover, patients with unmethylated glioblastoma respond poorly to this current standard treatment. This clinical trial evaluates the potential role of continuous, upfront use of Disulfiram in combination with Copper gluconate in enhancing temozolomide effect in the treatment of unmethylated Glioblastoma multiforme (GBM) patients.

Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme

A Phase II, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients With Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme

To determine 6 month PFS of patients with unmethylated glioblastoma treated with DSF-Cu in combination with concurrent radiation and temozolomide. This was assessed by the number of participants who did not have disease progression and were alive at 6 months.

Overall Survival will be assessed as a number of participants alive at 1 and 2 years.

Edmonton Symptom Assessment System - Revised (ESAS-r) questionnaire

Aurora Health Care

13 participants started the treatment and the only ones assessed for adverse events. All participants were included in all cause mortality.

Open-Label, Single Arm Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients with Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme

Open Label

Open-Label, Single Arm Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients with Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme.

DSF will be given at 125 mg (half of a 250 mg capsule) two times daily with meals. Cu gluconate will be taken with each dose of DSF at a dose of 2 mg (one capsule/tablet). The DSF total daily dose will be 250 mg per day, as lower dose may be associated with a higher MGMT inhibitory effect.

15 subjects consented, Age data was not collected for 2 participants - 1 subject was a screen fail and 1 subject withdrew before any planned intervention.

Age, Categorical

Both men and women and members of all races and ethnic groups are eligible for this trial

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

15 subjects consented, 1 subject was a screen fail and 1 subject withdrew before any planned intervention.

Manager of Oncology research

6 Months Progression Free Survival (PFS)

1 Year

2 Years

2 participants are not included here because 1 was a screen fail and 1 withdrew before starting treatment.

Overall Survival

Disease progression or required dose modification from all participants took them all off the study. No data was collected.

Quality of Life (QOL)

Overall Study

Patients will take a pill of disulfiram at a fixed dose of 250 mg with their evening meal. This dose of disulfiram used to treat alcoholism. We will start by administering 2 mg of copper as copper gluconate along with 250 mg disulfiram.

Patients must not consume beverages containing alcohol while taking disulfiram.

Commercially available. Copper gluconate has long been manufactured and sold as a food supplement. Copper gluconate should be taken separately from disulfiram, and if possible with breakfast.

Copper gluconate should not be administered to individuals with Wilson's disease or a family history of Wilson's disease.

Patients will receive 2 mg, 4mg, 6mg or 8mg daily

Kenneth Grossmann, MD, PhD

OBJECTIVES:

Primary Objectives

• Determine the safety and toxicity profile of co-administration of disulfiram and copper gluconate for the treatment of refractory malignancies that have metastasized to the liver.

Secondary Objectives

* Determine if disulfiram and copper gluconate induce measurable responses for the treatment of hepatic metastases from solid tumors.
* Qualitative assessment of the induction of S-glutathionylation in proteins of circulating leukocytes in patients treated with disulfiram and copper gluconate.

We have performed experimental studies demonstrating the anti-cancer efficacy of an old alcoholism treatment drug, disulfiram, combined with supplementation with certain metal ions. Together, disulfiram and metal ions induce S-glutathionylation of critical cancer cell proteins, inhibiting their activity, reducing tumor growth and inducing tumor cell apoptosis. The most active metal ion that can be paired with disulfiram appears to be the divalent metal ion copper. The purpose of this study is to determine the safety of co-administrating the thiocarbamate molecule disulfiram together with copper gluconate to patients with stage IV cancer metastatic to the liver.

Other investigators have studied the effect of disulfiram alone administered to patients with metastatic melanoma, and have observed no clinical benefit when disulfiram is administered without metal ion supplements (Dr. Patrick J. Farmer, University of California Irvine, personal communication).

We therefore propose that the optimum approach to using disulfiram as an antineoplastic agent is to co-administer it with metal ion supplements. While a number of metal ions can enhance the antineoplastic activity of disulfiram, including Zn2+, we have found Cu2+ to be the most active. This observation has been confirmed by others, who have shown that Cu2+ supplementation of growth media increases the pro-apoptotic (Cen 2004) and proteosomal-inhibitory (Chen 2006) activities of disulfiram. Compared to surrounding normal tissue, many cancer cells contain highly elevated levels of copper (Habib 1980; Rizk 1984; Turecky 1984; Diez 1989; Huang 1999; Kuo 2002; Nayak 2003). However, typical Western diets provide only 1 mg of copper daily, less than even the lower limit of 1.5 to 3.0 mg estimated safe and adequate daily dietary intake (ESADDI) of copper (Kelvay 1998; Failla 1999; Ma 2000; Pang 2001; Davis 2003). Therefore, dietary copper supplementation is likely necessary for disulfiram to be maximally effective as an antineoplastic drug. We project that the optimal dose of copper supplementation to pair with disulfiram is 8 mg elemental copper a day, the upper level of recommended daily copper (Institute for Medicine 2002), administered as copper gluconate, a substance generally regarded as safe (GRAS) (Code of Federal Regulation 2004). This amount would provide an eight-fold higher intake of copper than most American adults consume daily. Large amounts of ingested copper could result in hepatic failure and hemolysis similar to that seen with Wilson's disease, the rare genetic syndrome from hyperabsorption of copper. However, 8 mg of elemental copper has been previously administered to humans with few untoward effects (Pratt 1985; Olivares 1996; Rosado 2003; Mendez 2004; Araya 2005), and in one study even 20 mg of daily copper supplementation was well-tolerated (Araya 2004). Although copper intake is homeostatically regulated, with reduced gastrointestinal absorption at high intakes (Turnland 2005), chronic ingestion of as much as 60 mg elemental copper daily is likely toxic to normal individuals (O'Donohue 1993). In combining copper gluconate with disulfiram as an antineoplastic strategy, we would propose to administer the two in a fashion similar to that used for treatment of our patient with metastatic ocular melanoma, who experienced no diarrhea from zinc gluconate and disulfiram given at different times of the day (Figure 6.10). Copper gluconate containing up to 8 mg elemental copper would be given in the morning a half hour before breakfast, and disulfiram would be consumed with the evening meal. The rationale for separating administration of the two agents in time is to avoid producing gastrointestinal toxicity such as mucositis from complexation of copper by disulfiram in the gut.

Administered separately, we believe that disulfiram and Cu2+ will complex in vivo, forming a bis(diethyldi-thiocarbamato)-copper(II) complex (Johansson 1992) that will provide enhanced antineoplastic activity. It is also possible that metabolites of disulfiram have important activities (Loo 2004) that might also be enhanced by supplementation with copper. Administered orally, both disulfiram and Cu2+ will likely achieve high hepatic concentrations before distribution to other body tissues. This might suggest a utility of disulfiram and Cu2+ in treating primary hepatic tumors such as hepatomas, or secondary hepatic metastases from common malignancies such as colonic adenocarcinoma. The possibility of selective hepatic antineoplastic activity is supported by our experience with the patient suffering from metastatic ocular melanoma (Figure 6.10).

Subjects in this study will include those with advanced cancers metastatic to the liver who are not currently receiving or are eligible for other therapeutic approaches. When prescribed clinically for alcohol aversion, disulfiram is indicated in doses ranging from 125 mg to 500 mg orally each day. For safety reasons, we will initiate disulfiram use at a fixed dose of 250 mg per day, given with the evening meal. We will begin dosing with copper gluconate (2 mg elemental copper) given daily with the morning breakfast meal. These dose times are chosen to separate in time the administration of copper gluconate and disulfiram so that they will not be within the gastrointestinal lumen simultaneously, thereby preventing development of diarrhea and other side effects of mucositis from intraluminal formation of metal-thiocarbamate complexes. Copper gluconate doses will be increased in cohorts of 3 to 6 patients as detailed below as long as dose limiting toxicity is not observed. The maximum dose of copper gluconate to be administered will be the equivalent of 8 mg of elemental copper for the reasons outlined above. Subjects will be maintained on this regimen and followed for the duration of the protocol as long as they are not showing toxicity or disease progression, with periodic measurement of end-points outlined later. Major emphasis will be placed on following ALT and AST as indices of safety and serial abdominal imaging to determine the anatomic burden of hepatic metastases. During the protocol and for four weeks thereafter, subjects will be warned against the ingestion of ethanol and against exposure to alcohol-containing medications or consumer products.

We propose the gradually escalated dosing scheme above in anticipation of the most likely toxicity of the combined ingestion of disulfiram and copper supplements: hepatotoxicity. After gastrointestinal absorption, both agents are likely to be concentrated first in the liver. Therefore, the greatest risk will likely be an increase in hepatic transaminases. From experience with the combined administration of disulfiram and zinc supplements to a patient (Brar 2004) we believe that separating the times at which copper gluconate (morning breakfast meal) and disulfiram (evening meal) are ingested will prevent bothersome diarrhea or other symptoms of mucositis resulting from metal-thiocarbamate complexation within the bowel lumen. We anticipate that careful warning against the ingestion of ethanol-containing beverages or exposure to alcohol-containing consumer products will avert the risk of an inadvertent disulfiram ethanol reaction.

Phase I Study of Disulfiram and Copper Gluconate for the Treatment of Refractory Solid Tumors Involving the Liver

University of Utah

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

disulfiram and copper gluconate in combination

Patients will be instructed to self-administer disulfiram and copper gluconate twice daily at the assigned dose level. Both medications will be administered in 28-day cycles.

Douglas Sborov, MD

This is a phase I, open-label trial of disulfiram in combination with copper gluconate in patients with treatment-refractory multiple myeloma. The trial is designed to assess the Phase 2 Recommended Dose (RP2D) of disulfiram and copper gluconate in combination. The trial will open with dose escalation, followed to an expansion cohort to further characterize the safety and tolerance of the combination.

Dose escalation will utilize a standard 3+3 design and will test up to five dose levels. Dose levels will be separated into two sequential parts defined by the fixed dose of copper as copper gluconate administered with ascending doses of disulfiram. Part 1 of dose escalation will consist of dose levels 0 and 1 with the option to reduce to Dose Level -1 if Dose Level 0 is deemed intolerable. Part 2 will test dose levels 2 and 3. The Dose Level deemed to be the RP2D will be used in dose expansion.

A standard 3+3 dose escalation design will be used to determine the recommended phase 2 dose (RP2D) while ensuring the safety and tolerability of the treatment. Once the RP2D has been assigned in dose-escalation, an expansion cohort will open to the enrollment of 14 additional patients to further characterize the safety and tolerability of the study intervention.

Study of Disulfiram and Copper Gluconate in Patients With Treatment-Refractory Multiple Myeloma

A Phase I Study of Disulfiram and Copper Gluconate in Patients With Treatment-Refractory Multiple Myeloma

assess the recommended phase 2 dose of disulfiram in combination with copper as copper gluconate in subjects with relapse/refractory multiple myeloma.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
A Phase Ib Study of Intravenous Copper Loading With Oral Disulfiram in Metastatic, Castration Resistant Prostate Cancer	NCT02963051	Prostate Cancer	Copper Disulfiram Copper gluconat...	18 Years -	Duke University
Disulfiram/Copper With Concurrent Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma	NCT02715609	Glioblastoma Mu...	Disulfiram Copper Gluconat... Surgery Radiation Temozolomide	18 Years -	Washington University School of Medicine
Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme	NCT03363659	Glioblastoma Glioblastoma Mu...	Disulfiram Copper gluconat... Temozolomide	18 Years -	Aurora Health Care
Phase I Study of Disulfiram and Copper Gluconate for the Treatment of Refractory Solid Tumors Involving the Liver	NCT00742911	Cancer	Disulfiram Copper Gluconat...	18 Years -	University of Utah
Phase I Study of Disulfiram and Copper Gluconate for the Treatment of Refractory Solid Tumors Involving the Liver	NCT00742911	Cancer	Disulfiram Copper Gluconat...	18 Years -	University of Utah
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
Study of Disulfiram and Copper Gluconate in Patients With Treatment-Refractory Multiple Myeloma	NCT04521335	Multiple Myelom...	Disulfiram Copper Gluconat...	18 Years -	University of Utah

Spots Global Cancer Trial Database for copper gluconate