Clinical Trials /

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

NCT02532114

Description:

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Niclosamide</span> and <span class="go-doc-concept go-doc-intervention">Enzalutamide</span> in Treating Patients With Androgen Receptor Splice Variant-Positive, Castration-Resistant, Metastatic Prostate Cancer

Title

  • Brief Title: Niclosamide and Enzalutamide in Treating Patients With Androgen Receptor Splice Variant-Positive, Castration-Resistant, Metastatic Prostate Cancer
  • Official Title: A Phase I Study of Niclosamide in Combination With Enzalutamide in Men With Androgen Receptor Splice Variant Positive Castration-Resistant Prostate Cancer
  • Clinical Trial IDs

    NCT ID: NCT02532114

    ORG ID: 9390

    NCI ID: NCI-2015-01246

    Trial Conditions

    Hormone-Resistant Prostate Cancer

    Metastatic Prostate Carcinoma

    Recurrent Prostate Carcinoma

    Stage IV Prostate Adenocarcinoma

    Trial Interventions

    Drug Synonyms Arms
    Enzalutamide MDV3100, Xtandi Treatment (niclosamide, enzalutamide)
    Niclosamide Treatment (niclosamide, enzalutamide)

    Trial Purpose

    This phase I trial studies the side effects and best dose of niclosamide when given together
    with enzalutamide in treating patients with androgen receptor splice variant-positive,
    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.

    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 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.

    Trial Arms

    Name Type Description Interventions
    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. Enzalutamide, Niclosamide

    Eligibility 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)

    - Presence of an androgen receptor variant (AR-V) as documented by quantitative
    reverse-transcriptase-polymerase-chain-reaction (qRT-PCR)

    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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Male

    Primary Outcome Measures

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

    Recommended phase 2 dose

    Secondary Outcome Measures

    Half-life (T1/2) of niclosamide

    Maximum concentration (Cmax) of niclosamide

    Minimum concentration (Cmin) of niclosamide

    PSA response rate

    Steady state concentration (Css) of niclosamide

    Trial Keywords