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

NCT ID: NCT02532114

Last Updated: 2018-04-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2017-11-30

Brief Summary

This phase I trial studies the side effects and best dose of niclosamide when given together with enzalutamide in treating patients with castration resistant prostate cancer that has spread from the primary site to other places in the body. Androgens such as testosterone can cause the growth of prostate cancer cells. Drugs like enzalutamide block androgens from driving tumor growth; however, when androgen receptor splice variants are present, these drugs may not be effective. Niclosamide may decrease the amount of androgen receptor splice variant present within tumor cells, thus promoting the anti-tumor effects of enzalutamide. Giving niclosamide together with enzalutamide may be a better treatment for prostate cancer.

Detailed Description

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.

Conditions

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (niclosamide, enzalutamide)

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

Group Type: EXPERIMENTAL

Enzalutamide

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Niclosamide

Intervention Type: DRUG

Given PO

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Interventions

Enzalutamide

Given PO

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Niclosamide

Given PO

Intervention Type: DRUG

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

ASP9785; MDV3100; Xtandi

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Schweizer

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

References

Schweizer MT, Haugk K, McKiernan JS, Gulati R, Cheng HH, Maes JL, Dumpit RF, Nelson PS, Montgomery B, McCune JS, Plymate SR, Yu EY. A phase I study of niclosamide in combination with enzalutamide in men with castration-resistant prostate cancer. PLoS One. 2018 Jun 1;13(6):e0198389. doi: 10.1371/journal.pone.0198389. eCollection 2018.

Reference Type: DERIVED

PMID: 29856824 (View on PubMed)

Other Identifiers

NCI-2015-01246

Identifier Type: REGISTRY

Identifier Source: secondary_id

CC9390

Identifier Type: -

Identifier Source: secondary_id

9390

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P50CA097186

Identifier Type: NIH

Identifier Source: secondary_id

View Link

9390

Identifier Type: -

Identifier Source: org_study_id