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

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ClinicalTrials.gov Identifier: NCT02532114
Recruitment Status : Completed
First Posted : August 25, 2015
Last Update Posted : April 18, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

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.

Condition or disease Intervention/treatment Phase
Castration Levels of Testosterone Castration-Resistant Prostate Carcinoma Metastatic Prostate Carcinoma Recurrent Prostate Carcinoma Stage IV Prostate Adenocarcinoma Drug: Enzalutamide Other: Laboratory Biomarker Analysis Drug: Niclosamide Other: Pharmacological Study Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Niclosamide in Combination With Enzalutamide in Men With Castration-Resistant Prostate Cancer
Actual Study Start Date : December 31, 2015
Actual Primary Completion Date : November 30, 2017
Actual Study Completion Date : November 30, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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.
Drug: Enzalutamide
Given PO
Other Names:
  • ASP9785
  • MDV3100
  • Xtandi

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Niclosamide
Given PO

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. 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 ]
  2. Recommended phase 2 dose [ Time Frame: Up to 28 days ]

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02532114


Locations
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United States, Washington
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Michael Schweizer Fred Hutch/University of Washington Cancer Consortium

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT02532114     History of Changes
Other Study ID Numbers: 9390
NCI-2015-01246 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CC9390
9390 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
P50CA097186 ( U.S. NIH Grant/Contract )
First Posted: August 25, 2015    Key Record Dates
Last Update Posted: April 18, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
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Carcinoma
Prostatic Neoplasms
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Niclosamide
Anticestodal Agents
Antiplatyhelmintic Agents
Anthelmintics
Antiparasitic Agents
Anti-Infective Agents
Antinematodal Agents