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

NCT03123978 | Completed Phase 1 DMC FDA Drug

• 4 other identifiers: 914328UCDCC#264P30CA093373NCI-2017-00294
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the best dose and side effects of niclosamide when given together with enzalutamide in treating patients with castration-resistant prostate cancer that has come back or has spread to other places in the body. Androgens can cause the growth of prostate cancer cells. Hormone therapy using enzalutamide may fight prostate cancer by lowering the amount of androgen the body makes and/or blocking the use of androgen by the tumor cells. Niclosamide may block signals that enhance prostate cancer cell growth. Giving enzalutamide and niclosamide may work better in treating patients with castration-resistant prostate cancer.

Conditions

Metastatic Prostate Carcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

Keywords

castration resistant prostate cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events of grade 3 or higher assessed by National Cancer Institute Common Terminology Criteria for Adverse Events 4.0

  Adverse events and adverse events of grade 3 or higher will be listed for each patient and summarized by body system in a frequency table.

  Up to 4 weeks

• RP2D of niclosamide and enzalutamide

  Determination of dose limiting toxicity as graded according to NCI CTCAE 4.0.

  Up to 2 years

Secondary Outcomes (4)

• Overall survival

  Up to 5 years

• PFS

  Up to 5 years

• Rate of PSA response which is defined as >= 50% decrease

  Baseline up to 2 years

• Time to treatment failure

  Up to 2 years

Other Outcomes (1)

• Analysis of laboratory correlatives

  Up to 2 years

Study Arms (1)

Treatment (niclosamide, enzalutamide)

EXPERIMENTAL

Patients receive niclosamide PO BID and enzalutamide PO QD on weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Enzalutamide; Drug: Niclosamide

Interventions

Enzalutamide DRUG

Given PO

Also known as: ASP9785, MDV3100, Xtandi

Treatment (niclosamide, enzalutamide)

Niclosamide DRUG

Given PO

Treatment (niclosamide, enzalutamide)

Eligibility Criteria

• Age: 19 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed carcinoma of the prostate (CaP); CaP can be recurrent disease after definitive therapy (radical prostatectomy or radiation therapy) for localized CaP, or metastatic CaP
• Patients must have CaP deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation when applicable):
• Progression of unidimensionally measurable disease assessed within 42 days prior to initial administration of drug
• Progression of evaluable but not measurable disease assessed within 42 days prior to initial administration of drug for PSA evaluation and for imaging studies (e.g, bone scans)
• Rising PSA, defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) should be taken at least 7 days after the reference value; a third confirmatory PSA measure (2nd beyond the reference level) should be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA measurement is required to be taken and be greater than the second measure
• Measurable disease is not required:
• Patients who have measurable disease must have had X-rays, computed tomography (CT) scans or physical examinations used for tumor measurement completed within 28 days prior to initial administration of drug
• Patients must have non-measurable disease (such as nuclear medicine bone scans) and non-target lesions (such as PSA level) assessed within 28 days prior to initial administration of drug
• Soft tissue disease that has been radiated within two months prior to registration is not assessable as measurable disease; soft tissue disease that has been radiated two or more months prior to registration is assessable as measurable disease provided that the lesion has progressed following radiation; as the biology of previously irradiated tumors may be different from non-irradiated tumors, patients must have at least one measurable lesion outside the previously irradiated region in order to be considered to have measurable disease
• If PSA is the only indicator of disease without any evidence of metastasis, PSA value must be 5.0 or higher
• Expression of AR-V7 is not required as expression of AR-V7 can occur during enzalutamide and contribute to resistance to enzalutamide
• Patients must have been surgically or medically castrated; if the method of castration was luteinizing hormone-releasing hormone (LHRH) agonists (leuprolide or goserelin) or antagonists (degarelix), then the patient must be willing to continue the use of LHRH agonists or antagonists; serum testosterone must be at castration levels (\< 50 ng/dL) within 3 months prior to registration
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy should be deemed greater than 6 months
• Leukocytes \>= 3,000/mcL

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients who have received any other investigational agents within the preceding 4 weeks
• Patients taking herbal or other alternative medicines for the treatment of prostate cancer, including but not limited to saw palmetto, prostate cancer (PC)-SPES
• Patient has received enzalutamide for the treatment of prostate cancer; however, previous treatment with other hormonal therapy (bicalutamide, flutamide, nilutamide, abiraterone and ketoconazole) or chemotherapy (docetaxel, cabazitaxel or mitoxantrone) is allowed
• Other malignancies within the past 3 years except for adequately treated basal or squamous cell carcinomas of the skin or other stage 0 or I cancers
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide or PDMX1001/niclosamide
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
• Patients with an active, bleeding diathesis
• History of noncompliance to medical regimens
• Patients unwilling to or unable to comply with the protocol
• Patients with symptomatic metastatic prostate cancer experiencing moderate to severe pain, impaired organ function or spinal cord compression will be excluded from this study unless these issues have been addressed

Sponsors & Collaborators

• University of California, Davis: lead
• Pandomedx: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; Niclosamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Salicylanilides; Anilides; Amides; Organic Chemicals; Salicylamides; Aniline Compounds; Amines

Study Officials

• Mamta Parikh

  University of California, Davis

  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: April 18, 2017
• First Posted: April 21, 2017
• Study Start: January 9, 2017
• Primary Completion: January 14, 2022
• Study Completion: April 19, 2022
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (1)