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

April 16, 2018 updated by: University of Washington

A Phase I Study of Niclosamide in Combination With Enzalutamide in Men With Castration-Resistant Prostate Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: Enzalutamide
Given PO
Other Names:
  • Xtandi
  • MDV3100
  • ASP9785
Drug: Niclosamide
Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of dose-limiting toxicities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame: Up to 28 days
Up to 28 days
Recommended phase 2 dose
Time Frame: Up to 28 days
Up to 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Half-life of niclosamide
Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide
Mean niclosamide concentration versus time will be plotted for each dose cohort. Half-life will be reported as a mean for each dose cohort along with the observed ranges.
0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide
Maximum concentration of niclosamide
Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide
Mean niclosamide concentration versus time will be plotted for each dose cohort. maximum concentration will be reported as a mean for each dose cohort along with the observed ranges.
0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide
Minimum concentration of niclosamide
Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide
Mean niclosamide concentration versus time will be plotted for each dose cohort. Minimum concentration will be reported as a mean for each dose cohort along with the observed ranges.
0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide
PSA response rate
Time Frame: Baseline to up to 28 days
The percent change in PSA will be presented as a waterfall plot, with the rate of PSA response (i.e. >= 50% decline in PSA from baseline) reported as percentages with 95% confidence intervals.
Baseline to up to 28 days
Steady state concentration of niclosamide
Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide
Mean niclosamide concentration versus time will be plotted for each dose cohort. Steady state concentration will be reported as means for each dose cohort along with the observed ranges.
0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 31, 2015

Primary Completion (Actual)

November 30, 2017

Study Completion (Actual)

November 30, 2017

Study Registration Dates

First Submitted

August 12, 2015

First Submitted That Met QC Criteria

August 20, 2015

First Posted (Estimate)

August 25, 2015

Study Record Updates

Last Update Posted (Actual)

April 18, 2018

Last Update Submitted That Met QC Criteria

April 16, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9390 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
  • P30CA015704 (U.S. NIH Grant/Contract)
  • P50CA097186 (U.S. NIH Grant/Contract)
  • NCI-2015-01246 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • CC9390

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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