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Trial record 76 of 118 for:    DUTASTERIDE

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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Recruitment Status : Withdrawn (loss of funding)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

Tracking Information
First Submitted Date  ICMJE June 6, 2014
First Posted Date  ICMJE June 10, 2014
Last Update Posted Date January 26, 2015
Study Start Date  ICMJE September 2014
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 22, 2014)
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
Original Primary Outcome Measures  ICMJE
 (submitted: June 6, 2014)
Proportion of prostatectomy specimens with negative surgical margins [ Time Frame: 12 weeks ]
Proportion of prostatectomy specimens with negative surgical margins after 12 weeks of therapy
Change History Complete list of historical versions of study NCT02159690 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2014)
  • 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
  • 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
  • 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
  • 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).
  • 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.
  • 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)
  • 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.
  • Overall survival [ Time Frame: 2 years after last accrual ]
    The overall survival estimate two years after the last patient has accrued.
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2014)
  • Proportion of prostatectomy specimens with a pathologic complete response [ Time Frame: 12 weeks ]
    Proportion of prostatectomy specimens with a pathologic complete response after 12 weeks of therapy
  • 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
  • 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
  • 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, dutasteride and degarelix and an additional month of degarelix monotherapy (16 weeks total).
  • 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.
  • 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)
  • 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.
  • Overall survival [ Time Frame: 2 years after last accrual ]
    The overall survival estimate two years after the last patient has accrued.
  • 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
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase II Neoadjuvant Study of Enzalutamide, Abiraterone Acetate, Dutasteride and Degarelix in Men With Localized Prostate Cancer Pre-prostatectomy
Official Title  ICMJE A Phase II Neoadjuvant Study of Enzalutamide, Abiraterone Acetate, Dutasteride and Degarelix in Men With Localized Prostate Cancer Pre-prostatectomy
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Prostate Cancer
  • Localized Prostate Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: January 22, 2015)
0
Original Estimated Enrollment  ICMJE
 (submitted: June 6, 2014)
27
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02159690
Other Study ID Numbers  ICMJE Neoadj enz/abi/dut/deg
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kenneth Pienta, MD, Johns Hopkins University
Study Sponsor  ICMJE Kenneth Pienta, MD
Collaborators  ICMJE Prostate Cancer Foundation Norway
Investigators  ICMJE
Principal Investigator: Kenneth J Pienta, MD Johns Hopkins University
PRS Account Johns Hopkins University
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP