Copper Chloride, Disulfiram, and Copper Gluconate in Treating Patients with Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria

• Karnofsky performance status >= 70
• Life expectancy of >= 12 weeks as determined by treating investigator
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
• Platelets >= 80 x 10^9/L
• Hemoglobin (Hb) > 9 g/dl
• Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamate pyruvate transaminase (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 androgen deprivation therapy (ADT) using a luteinizing hormone-releasing hormone (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: * 2 consecutive PSA levels 50% or greater above the PSA nadir achieved on ADT and separated at least 1 week apart, OR * Computed tomography (CT) or magnetic resonance imaging (MRI) based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to Prostate Cancer Working Group 3 (PCWG3) criteria or Response Evaluation Criteria in Solid Tumors version 1.1 (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 2.0 ng/mL or greater, minimum 2 consecutive rising PSA levels with an interval of >= 1 week between each PSA level
• A minimum of 2 weeks elapsed off of antiandrogen therapy prior to registration (i.e. flutamide, nilutamide, and bicalutamide) without evidence of an anti-androgen withdrawal response; an anti-androgen withdrawal response is a PSA level at 2 weeks (or more) off of anti-androgen equal or higher than PSA level when anti-androgen therapy stopped
• For subjects in Groups B or C, previous use of at least one androgen pathway inhibitor (either abiraterone acetate or enzalutamide) for metastatic CRPC
• For subjects in Group A with neuroendocrine prostate cancer (NEPC), previous use of at least one platinum-containing chemotherapy regimen
• A minimum of 2 weeks off of enzalutamide or abiraterone, if applicable, prior to registration
• A minimum of 4 weeks from prior chemotherapy, including but not limited to, docetaxel, cabazitaxel, mitoxantrone, carboplatin, cisplatin, or estramustine; if applicable, prior to registration
• A minimum of 4 weeks from any major surgery prior to registration
• Ability to swallow, retain, and absorb oral medication
• Ability to understand and the willingness to sign a written informed consent document
• Willingness to abstain from alcohol or any alcohol-containing fluids for the duration of the study

Exclusion Criteria

• 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 blood pressure [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