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

Inclusion Criteria:

1. Age ≥ 18 years

2. Karnofsky performance status ≥ 70

3. Life expectancy of ≥ 12 weeks as determined by treating investigator

4. 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

5. 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.

6. Radiographic evidence of metastatic disease.

7. 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.

8. 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

- 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

9. 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.

10. For subjects in Groups B or C, previous use of at least one androgen pathway inhibitor
(either abiraterone acetate or enzalutamide) for metastatic CRPC

11. For subjects in Group A with NEPC, previous use of at least one platinum-containing
chemotherapy regimen.

12. A minimum of 2 weeks off of enzalutamide or abiraterone if applicable, prior to
registration.

13. A minimum of 4 weeks from prior chemotherapy, including but not limited to, docetaxel,
cabazitaxel, mitoxantrone, carboplatinum, cisplatin, or estramustine; if applicable,
prior to registration.

14. A minimum of 4 weeks from any major surgery prior to registration.

15. Ability to swallow, retain, and absorb oral medication.

16. Ability to understand and the willingness to sign a written informed consent document.

17. Willingness to abstain from alcohol or any alcohol-containing fluids for the duration
of the study.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from the study:

1. 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.)

2. Known history of Wilson's disease or a copper deficiency.

3. Uncontrolled hypertension (systolic BP >160 mmHg or diastolic BP > 95 mmHg) or other
medical condition that could jeopardize the assessment of toxicity on study.

4. Active or symptomatic viral hepatitis or chronic liver disease.

5. Known history of Hepatitis B Virus (HBV) or Hepatitis C (HCV) infection.

6. 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.

7. 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.

8. Corrected QT interval calculated by the Bazett formula (QTcB) >480 msec.

9. Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of death
within 24 months.

10. Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1.

11. Any condition which, in the opinion of the investigator, would preclude participation
in this trial.