Clinical Trials /

Abiraterone Acetate, Niclosamide, and Prednisone in Treating Patients With Hormone-Resistant Prostate Cancer

NCT02807805

Description:

This phase II trial studies the side effects and how well abiraterone acetate, niclosamide, and prednisone work in treating patients with hormone-resistant prostate cancer. Androgens can cause the growth of prostate cells. Hormone therapy using abiraterone acetate may fight prostate cancer by lowering the amount of androgen the body makes. Niclosamide is a drug that may block another signal that can cause prostate cancer cell growth. Prednisone is a drug that can help lessen inflammation. Giving abiraterone acetate, niclosamide, and prednisone may be a better treatment for patients with hormone-resistant prostate cancer.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abiraterone Acetate, Niclosamide, and Prednisone in Treating Patients With Hormone-Resistant Prostate Cancer
  • Official Title: A Phase II Study With a Lead-in Safety Phase of Abiraterone in Combination With PDMX1001/Niclosamide in Castration-Resistant Prostate Cancer (CRPC)

Clinical Trial IDs

  • ORG STUDY ID: UCDCC#260
  • SECONDARY ID: NCI-2016-00779
  • SECONDARY ID: UCDCC#260
  • SECONDARY ID: P30CA093373
  • NCT ID: NCT02807805

Conditions

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

Interventions

DrugSynonymsArms
Abiraterone AcetateCB7630, ZytigaTreatment (abiraterone acetate, niclosamide, prednisone)
NiclosamideTreatment (abiraterone acetate, niclosamide, prednisone)
Prednisone.delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisonum, Prednitone, Promifen, ServisoneTreatment (abiraterone acetate, niclosamide, prednisone)

Purpose

This phase II trial studies the side effects and how well abiraterone acetate, niclosamide, and prednisone work in treating patients with hormone-resistant prostate cancer. Androgens can cause the growth of prostate cells. Hormone therapy using abiraterone acetate may fight prostate cancer by lowering the amount of androgen the body makes. Niclosamide is a drug that may block another signal that can cause prostate cancer cell growth. Prednisone is a drug that can help lessen inflammation. Giving abiraterone acetate, niclosamide, and prednisone may be a better treatment for patients with hormone-resistant prostate cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the prostate-specific antigen (PSA) response that is a 50% or more reduction
      from the baseline.

      SECONDARY OBJECTIVES:

      I. To determine the overall response as determined by the Prostate Cancer Working Group 2
      criteria (PCWG2).

      II. To evaluate the progression-free survival (PFS) and overall survival of CRPC patients
      treated with PDMX1001/niclosamide (niclosamide), abiraterone (abiraterone acetate) and
      prednisone.

      III. To assess the toxicity of PDMX1001/niclosamide, abiraterone and prednisone given in
      combination.

      IV. 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:

      Patients receive abiraterone acetate orally (PO) once a day (QD), niclosamide PO twice a day
      (BID) and prednisone PO BID. 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 (abiraterone acetate, niclosamide, prednisone)ExperimentalPatients receive abiraterone acetate PO QD, niclosamide PO BID and prednisone PO BID. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
  • Abiraterone Acetate
  • Niclosamide
  • Prednisone

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed cancer of 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 (second [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, 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 and patients do not have any metastatic
                  disease, PSA value must be 5.0 or higher

          -  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 of 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 × institutional upper limit of normal

          -  Creatinine =< 1.5 x institutional upper limit of normal

          -  Men treated or enrolled on this protocol must also agree to use adequate
             contraception prior to the study, for the duration of study participation, and 4
             months after completion of abiraterone 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 are receiving any other investigational agents within the preceding 4
             weeks

          -  Patients on herbs or other alternative medicines for the treatment of prostate
             cancer, including but not limited to saw palmetto, PC-SPES

          -  Patient has received abiraterone or ketoconazole for the treatment of prostate
             cancer; however, previous treatment with other hormonal therapy (bicalutamide,
             enzalutamide, flutamide and nilutamide) 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

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to abiraterone 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 such as moderate to severe pain,
             impaired organ function or spinal cord compression will be excluded from this study
             unless these issues have been taken care of
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:PSA response rate
Time Frame:Up to 2 years
Safety Issue:
Description:Percent of patients achieving greater than or equal to 50% PSA declines following initiation of treatment

Secondary Outcome Measures

Measure:Incidence of dose limiting toxicity defined as any grade III non-hematologic toxicity not reversible to grade II or less within 96 hours, or any grade IV toxicity
Time Frame:4 weeks
Safety Issue:
Description:Graded according to 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.
Measure:Overall response as determined by PCWG2 criteria
Time Frame:From the time measurement criteria are met for complete response/partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years
Safety Issue:
Description:
Measure:Overall survival
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.
Measure:PFS
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. Will be compared with the historic control of abiraterone alone.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of California, Davis

Trial Keywords

  • castration resistant prostate cancer

Last Updated

September 8, 2016