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

NCT02963051 | Terminated Phase 1 FDA Drug

• 1 other identifier: Pro00071007
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

metastatic castrate-resistant prostate cancer (mCRPC); neuroendocrine prostate cancer (NEPC); adenocarcinoma castrate-resistant prostate cancer (CRPC); Copper; Disulfiram

Outcome Measures

Primary Outcomes (1)

• Number of adverse events

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

  Up to 2 years

Secondary Outcomes (5)

• Median radiographic progression free survival (PFS)

  Every 12 weeks, up to 2 years

• Amount of 64-Copper uptake by the tumor

  Baseline

• Change in PSA

  Every 4 weeks, up to 2 years

• Time to PSA nadir

  Every 4 weeks, up to 2 years

• Time to PSA progression

  Every 4 weeks, up to 2 years

Study Arms (3)

Neuroendocrine prostate cancer (NEPC)

EXPERIMENTAL

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.

Drug: Copper; Drug: Disulfiram; Drug: Copper gluconate

Adenocarcinoma CRPC with non-liver/peritoneal metastases

EXPERIMENTAL

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.

Drug: Copper; Drug: Disulfiram; Drug: Copper gluconate

Adenocarcinoma CRPC with liver and/or peritoneal mets

EXPERIMENTAL

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.

Drug: Copper; Drug: Disulfiram; Drug: Copper gluconate

Interventions

Copper DRUG

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

Also known as: Copper chloride

Adenocarcinoma CRPC with liver and/or peritoneal mets; Adenocarcinoma CRPC with non-liver/peritoneal metastases; Neuroendocrine prostate cancer (NEPC)

Disulfiram DRUG

80 mg three times a day Source of disulfiram: Cantex Pharmaceuticals

Also known as: Anatabuse

Adenocarcinoma CRPC with liver and/or peritoneal mets; Adenocarcinoma CRPC with non-liver/peritoneal metastases; Neuroendocrine prostate cancer (NEPC)

Copper gluconate DRUG

1.5 mg three times a day Source of copper gluconate: Cantex Pharmaceuticals

Adenocarcinoma CRPC with liver and/or peritoneal mets; Adenocarcinoma CRPC with non-liver/peritoneal metastases; Neuroendocrine prostate cancer (NEPC)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Karnofsky performance status ≥ 70
• Life expectancy of ≥ 12 weeks as determined by treating investigator
• Adequate laboratory parameters
• Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 80 x 109/L, Hb\>9 g/dL
• AST/SGOT and ALT/SGPT ≤ 2.5 x Institutional Upper Limit of Normal (ULN)
• Serum bilirubin ≤ 1.5 x Institutional ULN
• Serum creatinine ≤ 1.5 x Institutional ULN or 24-hour clearance ≥ 50 mL/min
• Histologically confirmed diagnosis of prostate cancer. Histologic variants of prostate cancer, including neuroendocrine features and small cell carcinoma of the prostate are included.If neuroendocrine prostate cancer is not biopsy proven, clinical evidence of neuroendocrine prostate cancer is acceptable for stratification into group A.
• Radiographic evidence of metastatic disease.
• Ongoing ADT using an LHRH agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix) must continue on therapy unless prior bilateral orchiectomy has been performed. OR Screening serum testosterone must be \<50 ng/dl.
• Evidence of disease progression on ADT as evidenced by one of the following:
• consecutive PSA levels 50% or greater above the PSA nadir achieved on ADT and separated at least 1 week apart, OR
• CT or MRI based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to PCWG3 criteria or RECIST 1.1 criteria, or at least 1 new bone scan lesion as compared to the most immediate prior radiologic studies, OR
• Absolute rise in PSA of 2.0ng/mL or greater, minimum 2 consecutive rising PSA levels with an interval of ≥ 1 week between each PSA level

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from the study:
• Symptomatic subjects who accept treatment with approved palliative or life-prolonging systemic therapies, including docetaxel and cabazitaxel chemotherapy. (Note: subjects who refuse chemotherapy or are not symptomatic or in immediate need for standard systemic therapies may be included.)
• Known history of Wilson's disease or a copper deficiency.
• Uncontrolled hypertension (systolic BP \>160 mmHg or diastolic BP \> 95 mmHg) or other medical condition that could jeopardize the assessment of toxicity on study.
• Active or symptomatic viral hepatitis or chronic liver disease.
• Known history of Hepatitis B Virus (HBV) or Hepatitis C (HCV) infection.
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of \< 50% at baseline.
• Symptomatic atrial fibrillation or other cardiac arrhythmia for which the therapy is not stable or requiring changes in therapy within 1 month of treatment initiation. Atrial fibrillation or other cardiac arrhythmia which is clinically stable on stable therapy is allowed.
• Corrected QT interval calculated by the Bazett formula (QTcB) \>480 msec.
• Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of death within 24 months.
• Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1.
• Any condition which, in the opinion of the investigator, would preclude participation in this trial.

Sponsors & Collaborators

• Daniel George, MD: lead
• Give 1 For Dad Campaign: collaborator
• The V Foundation for Cancer Research: collaborator
• Peter Michael Foundation: collaborator
• Cantex Pharmaceuticals: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Copper; Disulfiram; Gluconates

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds; Sugar Acids; Hydroxy Acids; Carbohydrates

Study Officials

• Daniel George, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: November 10, 2016
• First Posted: November 15, 2016
• Study Start: July 11, 2017
• Primary Completion: December 30, 2018
• Study Completion: February 1, 2020
• Last Updated: September 16, 2021

Record last verified: 2021-09

Locations

US (1)