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

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ClinicalTrials.gov Identifier: NCT03123978
Recruitment Status : Recruiting
First Posted : April 21, 2017
Last Update Posted : May 23, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Pandomedx
Information provided by (Responsible Party):
Mamta Parikh, University of California, Davis

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.

Condition or disease Intervention/treatment Phase
Metastatic Prostate Carcinoma Recurrent Prostate Carcinoma Stage IV Prostate Cancer Drug: Enzalutamide Drug: Niclosamide Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the safety of niclosamide (PDMX1001/niclosamide) and enzalutamide in patients with castration-resistant prostate cancer (CRPC).

II. To determine the recommended phase II dose (RP2D) of PDMX1001/niclosamide and enzalutamide for the treatment of patients with CRPC.

SECONDARY OBJECTIVES:

I. To determine the pharmacokinetics of PDMX1001/niclosamide. II. To determine the number of patients who have a prostate-specific antigen (PSA) response that is a 50% or more reduction from the baseline.

III. To identify overall responses as determined by the Prostate Cancer Working Group 2 (PCWG2) criteria.

IV. To evaluate the progression-free survival (PFS) of CRPC patients treated with PDMX1001/niclosamide and enzalutamide.

V. To evaluate molecular correlatives for patient response and outcomes through the analysis of patient baseline tumor specimens (diagnostic biopsy) along with serial blood specimens.

OUTLINE: This is a dose-escalation study of niclosamide.

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

After completion of study treatment, patients are followed up for 3 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Safety Trial of Enzalutamide in Combination With PDMX1001/Niclosamide in Castration-Resistant Prostate Cancer (CRPC)
Actual Study Start Date : January 9, 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : January 2021

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 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
Given PO
Other Names:
  • ASP9785
  • MDV3100
  • Xtandi

Drug: Niclosamide
Given PO




Primary Outcome Measures :
  1. Incidence of adverse events of grade 3 or higher assessed by National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 [ Time Frame: Up to 4 weeks ]
    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.

  2. RP2D of niclosamide and enzalutamide [ Time Frame: Up to 2 years ]
    Determination of dose limiting toxicity as graded according to NCI CTCAE 4.0.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Up to 5 years ]
    Will be estimated using the product-limit method of Kaplan and Meier; medians and 95% confidence intervals will be computed.

  2. PFS [ Time Frame: Up to 5 years ]
    Will be estimated using the product-limit method of Kaplan and Meier; medians and 95% confidence intervals will be computed.

  3. Rate of PSA response which is defined as >= 50% decrease [ Time Frame: Baseline up to 2 years ]
    The characteristics of the study participants will be summarized using frequencies and percentages for categorical variables and descriptive statistics (mean, standard deviation, median, minimum, maximum) for numeric variables. The proportion of participants who experience a PSA response will be computed, along with the exact 95% confidence interval.

  4. Time to treatment failure [ Time Frame: Up to 2 years ]
    Will be estimated using the product-limit method of Kaplan and Meier; medians and 95% confidence intervals will be computed.


Other Outcome Measures:
  1. Analysis of laboratory correlatives [ Time Frame: Up to 2 years ]
    Will be performed between patients who respond and those who do not respond, and between specimens obtained during response and those specimens obtained during resistance in the same patients. Will be descriptive and exploratory.



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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal
  • Creatinine =< 1.5 x institutional upper limit of normal
  • Men treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of enzalutamide and PDMX1001/niclosamide administration
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • 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

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): NCT03123978


Locations
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United States, California
University of California Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Mamta Parikh    916-734-3772    mbparikh@ucdavis.edu   
Principal Investigator: Mamta Parikh         
Sponsors and Collaborators
Mamta Parikh
National Cancer Institute (NCI)
Pandomedx
Investigators
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Principal Investigator: Mamta Parikh University of California, Davis

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Responsible Party: Mamta Parikh, Principal Investigator, University of California, Davis
ClinicalTrials.gov Identifier: NCT03123978     History of Changes
Other Study ID Numbers: 914328
UCDCC#264 ( Other Identifier: UC Davis IRB )
P30CA093373 ( U.S. NIH Grant/Contract )
NCI-2017-00294 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: April 21, 2017    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mamta Parikh, University of California, Davis:
castration resistant prostate cancer
Additional relevant MeSH terms:
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Carcinoma
Prostatic Neoplasms
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