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Trial record 76 of 117 for:    DUTASTERIDE

A Phase II Neoadjuvant Study of Enzalutamide, Abiraterone Acetate, Dutasteride and Degarelix in Men With Localized Prostate Cancer Pre-prostatectomy

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ClinicalTrials.gov Identifier: NCT02159690
Recruitment Status : Withdrawn (loss of funding)
First Posted : June 10, 2014
Last Update Posted : January 26, 2015
Sponsor:
Collaborator:
Prostate Cancer Foundation Norway
Information provided by (Responsible Party):
Kenneth Pienta, MD, Johns Hopkins University

Brief Summary:

This study investigates the pathologic effects of the combination of enzalutamide, abiraterone acetate, dutasteride, and degarelix when given for 12 weeks prior to prostatectomy in men with localized prostate cancer.

Enzalutamide, an androgen receptor (AR) antagonist, blocks binding of testosterone to the AR as well as preventing nuclear translocation of the AR and DNA binding. Abiraterone acetate inhibits the CYP17 pathway, which is involved in the formation of androgens. Dutasteride is a 5-alpha-reductase inhibitor which blocks conversion of testosterone to dihydrotestosterone. Degarelix, a gonadotropin-releasing hormone (GnRH) antagonist, binds to GnRH receptors on the pituitary gland thus suppressing testosterone release from the testes.

Therefore it is hypothesized that the combination of enzalutamide, abiraterone acetate, dutasteride, and degarelix will result in near-complete AR inhibition and produce favorable pathologic changes after 12 weeks of therapy.


Condition or disease Intervention/treatment Phase
Prostate Cancer Localized Prostate Cancer Drug: Enzalutamide Drug: Abiraterone acetate Drug: Prednisone Drug: Dutasteride Drug: Degarelix Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Neoadjuvant Study of Enzalutamide, Abiraterone Acetate, Dutasteride and Degarelix in Men With Localized Prostate Cancer Pre-prostatectomy
Study Start Date : September 2014
Actual Primary Completion Date : January 2015
Actual Study Completion Date : January 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer


Intervention Details:
  • Drug: Enzalutamide
    160mg
    Other Names:
    • MDV3100
    • Xtandi
  • Drug: Abiraterone acetate
    1000mg
    Other Name: Zytiga
  • Drug: Prednisone
    5mg twice daily (to blunt mineralocorticoid side effects from abiraterone)
    Other Name: Deltasone
  • Drug: Dutasteride
    0.5mg
    Other Name: Avodart
  • Drug: Degarelix
    240mg SC loading dose on day 1, then three 80mg SC injections every 4 weeks thereafter
    Other Name: Firmagon


Primary Outcome Measures :
  1. Proportion of prostatectomy specimens with a complete response rate [ Time Frame: 12 weeks ]
    Proportion of prostatectomy specimens with complete response rate after 12 weeks of therapy


Secondary Outcome Measures :
  1. Proportion of prostatectomy specimens with a negative surgical margin rate [ Time Frame: 12 weeks ]
    Proportion of prostatectomy specimens with a negative surgical margin rate after 12 weeks of therapy

  2. Proportion of prostatectomy specimens with a near-pathologic complete response [ Time Frame: 12 weeks ]
    Proportion of prostatectomy specimens with a near-pathologic complete response (<=5mm of residual tumor) after 12 weeks of therapy

  3. Proportion of prostatectomy specimens with pathologic T3 disease [ Time Frame: 12 weeks ]
    Proportion of prostatectomy specimens with pathologic T3 disease after 12 weeks of therapy

  4. Change in immunologic parameters (TREC levels and antibody responses) [ Time Frame: 16 weeks ]
    Change in immunologic parameters (TREC levels and antibody responses) after 12 weeks of enzalutamide, abiraterone acetate, dutasteride and degarelix and an additional month of degarelix monotherapy (16 weeks total).

  5. Proportion of radiographic disappearance of MRI detectable significant prostate nodules [ Time Frame: 12 weeks ]
    Proportion of radiographic disappearance of MRI detectable significant prostate nodules after 12 weeks of therapy.

  6. Proportion of men who receive adjuvant radiation therapy within 1 year of prostatectomy [ Time Frame: 64 weeks ]
    Proportion of men who receive adjuvant radiation therapy within 1 year of prostatectomy (12 weeks of therapy + 1 year = 64 weeks)

  7. PSA progression free survival [ Time Frame: 2 years after last accrual ]
    The biochemical (i.e. PSA) progression free survival estimate two years after the last patient has accrued.

  8. Overall survival [ Time Frame: 2 years after last accrual ]
    The overall survival estimate two years after the last patient has accrued.

  9. Incidence and severity of adverse events [ Time Frame: 16 weeks ]
    Safety as assessed by the incidence and severity of adverse events and serious adverse events graded according to the National Cancer Institute - Common Terminology Criteria for adverse events (CTCAE) version 4.0

  10. Exploratory biomarkers assessment [ Time Frame: 16 weeks ]
    Exploratory biomarker Assessment. Examples of these may include, but are not limited to: assessment for genomic PTEN loss via fluorescence in situ hybridization (FISH), PTEN immunohistochemistry (IHC), assessment for alteration in MYC/chromosome 8q24 via FISH, RNAseq analysis, serum drug/androgen levels and intraprostatic drug/androgen levels.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing and able to provide written informed consent.
  2. Age ≥ 18 years
  3. Eastern cooperative group (ECOG) performance status ≤2
  4. Documented histologically confirmed adenocarcinoma of the prostate
  5. Willing to undergo prostatectomy as primary treatment for localized prostate cancer
  6. High risk prostate cancer (per NCCN criteria): Gleason score 8-10 or T3a or PSA > 20 ng/mL -Or- Very-high risk prostate cancer (per NCCN criteria): T3b -T4
  7. Serum testosterone ≥150 ng/dL
  8. Able to swallow the study drugs whole as tablets
  9. Willing to take abiraterone acetate on an empty stomach (no food should be consumed at least two hours before and for one hour after dosing).
  10. Willing to use a condom if having sex with a pregnant woman, or use a condom and another effective method of birth control if having sex with a woman of child-bearing potential. These measures are required during and for one week after treatment with abiraterone.

Exclusion Criteria:

  1. Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)
  2. Prior use of enzalutamide or abiraterone acetate
  3. Prior or ongoing systemic therapy for prostate cancer including, but not limited to:

    1. Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)
    2. CYP-17 inhibitors (e.g. ketoconazole)
    3. Antiandrogens (e.g. bicalutamide, nilutamide)
    4. Second generation antiandrogens (e.g. enzalutamide, ARN-509)
    5. Immunotherapy (e.g. sipuleucel-T, ipilimumab)
    6. Chemotherapy (e.g. docetaxel, cabazitaxel)
  4. Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study.
  5. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
  6. Abnormal bone marrow function [absolute neutrophil count (ANC)<1500/mm3, platelet count <100,000/mm3, hemoglobin <9 g/dL]
  7. Abnormal liver function (bilirubin, AST, ALT ≥ 3 x upper limit of normal)
  8. Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal)
  9. Abnormal cardiac function as manifested by NYHA (New York Heart Association) class III or IV heart failure or history of a prior myocardial infarction (MI) within the last five years prior to enrollment in the study.
  10. History of prior cardiac arrhythmia.

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): NCT02159690


Locations
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United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Kenneth Pienta, MD
Prostate Cancer Foundation Norway
Investigators
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Principal Investigator: Kenneth J Pienta, MD Johns Hopkins University

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Responsible Party: Kenneth Pienta, MD, Principal Investigator, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT02159690     History of Changes
Other Study ID Numbers: Neoadj enz/abi/dut/deg
First Posted: June 10, 2014    Key Record Dates
Last Update Posted: January 26, 2015
Last Verified: January 2015
Keywords provided by Kenneth Pienta, MD, Johns Hopkins University:
prostate cancer
prostatectomy
localized prostate cancer
Additional relevant MeSH terms:
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Dutasteride
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Abiraterone Acetate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors
5-alpha Reductase Inhibitors