NCT02532114

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Dec 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 12, 2015

Completed
13 days until next milestone

First Posted

Study publicly available on registry

August 25, 2015

Completed
4 months until next milestone

Study Start

First participant enrolled

December 31, 2015

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2017

Completed
Last Updated

April 18, 2018

Status Verified

April 1, 2018

Enrollment Period

1.9 years

First QC Date

August 12, 2015

Last Update Submit

April 16, 2018

Conditions

Castration Levels of TestosteroneCastration-Resistant Prostate CarcinomaMetastatic Prostate CarcinomaRecurrent Prostate CarcinomaStage IV Prostate Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

  • Incidence of dose-limiting toxicities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Up to 28 days

  • Recommended phase 2 dose

    Up to 28 days

Secondary Outcomes (5)

  • Half-life of niclosamide

    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

    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

    0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide

  • PSA response rate

    Baseline to up to 28 days

  • Steady state concentration of niclosamide

    0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide

Study Arms (1)

Treatment (niclosamide, enzalutamide)

EXPERIMENTAL

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

Drug: EnzalutamideOther: Laboratory Biomarker AnalysisDrug: NiclosamideOther: Pharmacological Study

Interventions

EnzalutamideDRUG

Given PO

Also known as: ASP9785, MDV3100, Xtandi
Treatment (niclosamide, enzalutamide)
Laboratory Biomarker AnalysisOTHER

Correlative studies

Treatment (niclosamide, enzalutamide)
NiclosamideDRUG

Given PO

Treatment (niclosamide, enzalutamide)
Pharmacological StudyOTHER

Correlative studies

Treatment (niclosamide, enzalutamide)

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

  • 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.

    PMID: 29856824DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamideNiclosamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

SalicylanilidesAnilidesAmidesOrganic ChemicalsSalicylamidesAniline CompoundsAmines

Study Officials

  • Michael Schweizer

    Fred Hutch/University of Washington Cancer Consortium

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 12, 2015

First Posted

August 25, 2015

Study Start

December 31, 2015

Primary Completion

November 30, 2017

Study Completion

November 30, 2017

Last Updated

April 18, 2018

Record last verified: 2018-04

Locations

US(1)