Expired Study
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Seattle, Washington 98109


Purpose:

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 summary:

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.


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


Study is Available At:


Original ID:

9390


NCT ID:

NCT02532114


Secondary ID:

NCI-2015-01246


Study Acronym:


Brief Title:

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


Official Title:

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


Overall Status:

Completed


Study Phase:

Phase 1


Genders:

Male


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of Washington


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

5


Enrollment Type:

Actual


Overall Contact Information

Official Name:Michael Schweizer
Principal Investigator
Fred Hutch/University of Washington Cancer Consortium

Study Dates

Start Date:December 31, 2015
Completion Date:November 30, 2017
Completion Type:Actual
Primary Completion Date:November 30, 2017
Primary Completion Type:Actual
Verification Date:April 2018
Last Changed Date:April 16, 2018
First Received Date:August 12, 2015

Study Outcomes

Outcome Type:Secondary Outcome
Measure: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
Safety Issues:False
Description: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.
Outcome Type:Secondary Outcome
Measure:PSA response rate
Time Frame:Baseline to up to 28 days
Safety Issues:False
Description: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.
Outcome Type:Secondary Outcome
Measure: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
Safety Issues:False
Description: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.
Outcome Type:Secondary Outcome
Measure: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
Safety Issues:False
Description: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.
Outcome Type:Secondary Outcome
Measure: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
Safety Issues:False
Description: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.
Outcome Type:Primary Outcome
Measure:Recommended phase 2 dose
Time Frame:Up to 28 days
Safety Issues:False
Outcome Type:Primary Outcome
Measure: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
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:Enzalutamide
Description:Given PO
Arm Name:Treatment (niclosamide, enzalutamide)
Other Name:ASP9785
Intervention Type:Other
Name:Laboratory Biomarker Analysis
Description:Correlative studies
Arm Name:Treatment (niclosamide, enzalutamide)
Intervention Type:Drug
Name:Niclosamide
Description:Given PO
Arm Name:Treatment (niclosamide, enzalutamide)
Intervention Type:Other
Name:Pharmacological Study
Description:Correlative studies
Arm Name:Treatment (niclosamide, enzalutamide)

Study Arms

Study Arm Type:Experimental
Arm Name:Treatment (niclosamide, enzalutamide)
Description:Patients receive niclosamide PO TID and enzalutamide PO daily. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of Washington
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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