Back to resultsA Phase II Neoadjuvant Study of Enzalutamide, Abiraterone Acetate, Dutasteride and Degarelix in Men With Localized Prostate Cancer Pre-prostatectomy
Primary Purpose
Prostate Cancer, Localized Prostate Cancer
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Enzalutamide
Abiraterone acetate
Prednisone
Dutasteride
Degarelix
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring prostate cancer, prostatectomy, localized prostate cancer
Eligibility Criteria
Inclusion Criteria:
- Willing and able to provide written informed consent.
- Age ≥ 18 years
- Eastern cooperative group (ECOG) performance status ≤2
- Documented histologically confirmed adenocarcinoma of the prostate
- Willing to undergo prostatectomy as primary treatment for localized prostate cancer
- 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
- Serum testosterone ≥150 ng/dL
- Able to swallow the study drugs whole as tablets
- 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).
- 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:
- Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)
- Prior use of enzalutamide or abiraterone acetate
Prior or ongoing systemic therapy for prostate cancer including, but not limited to:
- Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)
- CYP-17 inhibitors (e.g. ketoconazole)
- Antiandrogens (e.g. bicalutamide, nilutamide)
- Second generation antiandrogens (e.g. enzalutamide, ARN-509)
- Immunotherapy (e.g. sipuleucel-T, ipilimumab)
- Chemotherapy (e.g. docetaxel, cabazitaxel)
- 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.
- Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
- Abnormal bone marrow function [absolute neutrophil count (ANC)<1500/mm3, platelet count <100,000/mm3, hemoglobin <9 g/dL]
- Abnormal liver function (bilirubin, AST, ALT ≥ 3 x upper limit of normal)
- Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal)
- 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.
- History of prior cardiac arrhythmia.
Sites / Locations
- Johns Hopkins Hospital
Outcomes
Primary Outcome Measures
Proportion of prostatectomy specimens with a complete response rate
Proportion of prostatectomy specimens with complete response rate after 12 weeks of therapy
Secondary Outcome Measures
Proportion of prostatectomy specimens with a negative surgical margin rate
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
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
Proportion of prostatectomy specimens with pathologic T3 disease after 12 weeks of therapy
Change in immunologic parameters (TREC levels and antibody responses)
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
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
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
The biochemical (i.e. PSA) progression free survival estimate two years after the last patient has accrued.
Overall survival
The overall survival estimate two years after the last patient has accrued.
Incidence and severity of adverse events
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
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.
Full Information
NCT ID
NCT02159690
First Posted
June 6, 2014
Last Updated
January 22, 2015
Sponsor
Kenneth Pienta, MD
Collaborators
Prostate Cancer Foundation Norway
1. Study Identification
Unique Protocol Identification Number
NCT02159690
Brief Title
A Phase II Neoadjuvant Study of Enzalutamide, Abiraterone Acetate, Dutasteride and Degarelix in Men With Localized Prostate Cancer Pre-prostatectomy
Official Title
A Phase II Neoadjuvant Study of Enzalutamide, Abiraterone Acetate, Dutasteride and Degarelix in Men With Localized Prostate Cancer Pre-prostatectomy
Study Type
Interventional
2. Study Status
Record Verification Date
January 2015
Overall Recruitment Status
Withdrawn
Why Stopped
loss of funding
Study Start Date
September 2014 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Kenneth Pienta, MD
Collaborators
Prostate Cancer Foundation Norway
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Localized Prostate Cancer
Keywords
prostate cancer, prostatectomy, localized prostate cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Enzalutamide
Other Intervention Name(s)
MDV3100, Xtandi
Intervention Description
160mg
Intervention Type
Drug
Intervention Name(s)
Abiraterone acetate
Other Intervention Name(s)
Zytiga
Intervention Description
1000mg
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
Deltasone
Intervention Description
5mg twice daily (to blunt mineralocorticoid side effects from abiraterone)
Intervention Type
Drug
Intervention Name(s)
Dutasteride
Other Intervention Name(s)
Avodart
Intervention Description
0.5mg
Intervention Type
Drug
Intervention Name(s)
Degarelix
Other Intervention Name(s)
Firmagon
Intervention Description
240mg SC loading dose on day 1, then three 80mg SC injections every 4 weeks thereafter
Primary Outcome Measure Information:
Title
Proportion of prostatectomy specimens with a complete response rate
Description
Proportion of prostatectomy specimens with complete response rate after 12 weeks of therapy
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Proportion of prostatectomy specimens with a negative surgical margin rate
Description
Proportion of prostatectomy specimens with a negative surgical margin rate after 12 weeks of therapy
Time Frame
12 weeks
Title
Proportion of prostatectomy specimens with a near-pathologic complete response
Description
Proportion of prostatectomy specimens with a near-pathologic complete response (<=5mm of residual tumor) after 12 weeks of therapy
Time Frame
12 weeks
Title
Proportion of prostatectomy specimens with pathologic T3 disease
Description
Proportion of prostatectomy specimens with pathologic T3 disease after 12 weeks of therapy
Time Frame
12 weeks
Title
Change in immunologic parameters (TREC levels and antibody responses)
Description
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).
Time Frame
16 weeks
Title
Proportion of radiographic disappearance of MRI detectable significant prostate nodules
Description
Proportion of radiographic disappearance of MRI detectable significant prostate nodules after 12 weeks of therapy.
Time Frame
12 weeks
Title
Proportion of men who receive adjuvant radiation therapy within 1 year of prostatectomy
Description
Proportion of men who receive adjuvant radiation therapy within 1 year of prostatectomy (12 weeks of therapy + 1 year = 64 weeks)
Time Frame
64 weeks
Title
PSA progression free survival
Description
The biochemical (i.e. PSA) progression free survival estimate two years after the last patient has accrued.
Time Frame
2 years after last accrual
Title
Overall survival
Description
The overall survival estimate two years after the last patient has accrued.
Time Frame
2 years after last accrual
Title
Incidence and severity of adverse events
Description
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
Time Frame
16 weeks
Title
Exploratory biomarkers assessment
Description
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.
Time Frame
16 weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Willing and able to provide written informed consent.
Age ≥ 18 years
Eastern cooperative group (ECOG) performance status ≤2
Documented histologically confirmed adenocarcinoma of the prostate
Willing to undergo prostatectomy as primary treatment for localized prostate cancer
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
Serum testosterone ≥150 ng/dL
Able to swallow the study drugs whole as tablets
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).
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:
Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)
Prior use of enzalutamide or abiraterone acetate
Prior or ongoing systemic therapy for prostate cancer including, but not limited to:
Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)
CYP-17 inhibitors (e.g. ketoconazole)
Antiandrogens (e.g. bicalutamide, nilutamide)
Second generation antiandrogens (e.g. enzalutamide, ARN-509)
Immunotherapy (e.g. sipuleucel-T, ipilimumab)
Chemotherapy (e.g. docetaxel, cabazitaxel)
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.
Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
Abnormal bone marrow function [absolute neutrophil count (ANC)<1500/mm3, platelet count <100,000/mm3, hemoglobin <9 g/dL]
Abnormal liver function (bilirubin, AST, ALT ≥ 3 x upper limit of normal)
Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal)
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.
History of prior cardiac arrhythmia.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kenneth J Pienta, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase II Neoadjuvant Study of Enzalutamide, Abiraterone Acetate, Dutasteride and Degarelix in Men With Localized Prostate Cancer Pre-prostatectomy
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