Niclosamide and Enzalutamide in Treating Patients With Castration-Resistant, Metastatic Prostate Cancer

PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of three-times-daily (TID) oral niclosamide combined
with enzalutamide in men with castration-resistant prostate cancer (CRPC) that has progressed
on abiraterone (abiraterone acetate).

SECONDARY OBJECTIVES:

I. Determine the effect of niclosamide plus enzalutamide on androgen receptor splice variant
(AR-V) expression as determined by quantitative
reverse-transcriptase-polymerase-chain-reaction (qRT-PCR).

II. Determine the pharmacokinetic profile of three-times-daily (TID) oral niclosamide in men
with castration-resistant prostate cancer (CRPC) that has progressed on abiraterone.

III. Determine the prostate specific antigen (PSA) response rate (i.e. proportion of subjects
with >= 50% decline in PSA from pre-study baseline) after 28-days of niclosamide plus
enzalutamide.

IV. Determine the effect of niclosamide plus enzalutamide on protein expression and the
transcriptional program of circulating tumor cells.

OUTLINE: This is a dose-escalation study of niclosamide.

Patients receive niclosamide orally (PO) TID and enzalutamide PO daily. Treatment continues
for 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at days 58 and 88.

Inclusion Criteria:

- Have signed an informed consent document indicating that the subject understands the
purpose of and procedures required for the study and are willing to participate in the
study

- Be willing/able to adhere to the prohibitions and restrictions specified in this
protocol

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Documented histologically confirmed adenocarcinoma of the prostate

- Patient must have evidence of castration resistant prostate cancer as evidenced by a
confirmed rising PSA (per Prostate Cancer Working Group 2 [PCWG2] criteria) and a
castrate serum testosterone level (i.e. =< 50 mg/dL)

- Patient must be eligible for treatment with enzalutamide

- Patient must have previously progressed on abiraterone (either by PCWG2 criteria or
Response Evaluation Criteria in Solid Tumors [RECIST] criteria)

- Documented metastatic disease on bone scan, computed tomography (CT) scan or magnetic
resonance imaging (MRI)

Exclusion Criteria:

- Have known allergies, hypersensitivity, or intolerance to enzalutamide or niclosamide
or their excipients

- Ongoing systemic therapy (other than a gonadotropin releasing hormone [GnRH]
agonist/antagonist) for prostate cancer including, but not limited to:

- Cytochrome P450, family 17 (CYP-17) inhibitors (e.g. ketoconazole, abiraterone)

- Antiandrogens (e.g. bicalutamide, nilutamide)

- Second generation antiandrogens (e.g. ARN-509)

- Note: patients receiving ongoing treatment with enzalutamide will be allowed
to join the study

- Immunotherapy (e.g. sipuleucel-T, ipilimumab)

- Chemotherapy (e.g. docetaxel, cabazitaxel)

- Radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium-153)

- Have any condition that, in the opinion of the investigator, would compromise the
well-being of the subject or the study or prevent the subject from meeting or
performing study requirements

- Any psychological, familial, sociological, or geographical condition that could
potentially interfere with compliance with the study protocol and follow-up schedule

- Severe hepatic impairment (Child-Pugh class C)

- Severe renal impairment (creatinine clearance =< 30 ml/min)

- History of prior seizures

- Central nervous system metastases

- Symptomatic patients who, in the opinion of the investigator, may benefit from
docetaxel-based chemotherapy