Clinical Trials /

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

NCT03123978

Description:

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Enzalutamide and Niclosamide in Treating Patients With Recurrent or Metastatic Castration-Resistant Prostate Cancer
  • Official Title: A Safety Trial of Enzalutamide in Combination With PDMX1001/Niclosamide in Castration-Resistant Prostate Cancer (CRPC)

Clinical Trial IDs

  • ORG STUDY ID: UCDCC#264
  • SECONDARY ID: NCI-2017-00294
  • SECONDARY ID: UCDCC#264
  • SECONDARY ID: P30CA093373
  • NCT ID: NCT03123978

Conditions

  • Metastatic Prostate Carcinoma
  • Recurrent Prostate Carcinoma
  • Stage IV Prostate Cancer

Interventions

DrugSynonymsArms
EnzalutamideASP9785, MDV3100, XtandiTreatment (niclosamide, enzalutamide)
NiclosamideTreatment (niclosamide, enzalutamide)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (niclosamide, enzalutamide)ExperimentalPatients 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.
  • Enzalutamide
  • Niclosamide

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Up to 5 years
Safety Issue:
Description:Will be estimated using the product-limit method of Kaplan and Meier; medians and 95% confidence intervals will be computed.
Measure:PFS
Time Frame:Up to 5 years
Safety Issue:
Description:Will be estimated using the product-limit method of Kaplan and Meier; medians and 95% confidence intervals will be computed.
Measure:Rate of PSA response which is defined as >= 50% decrease
Time Frame:Baseline up to 2 years
Safety Issue:
Description: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.
Measure:Time to treatment failure
Time Frame:Up to 2 years
Safety Issue:
Description:Will be estimated using the product-limit method of Kaplan and Meier; medians and 95% confidence intervals will be computed.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of California, Davis

Trial Keywords

  • castration resistant prostate cancer

Last Updated

April 18, 2017