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

Phase 2

Withdrawn

• Conditions: Prostate Cancer; Localized Prostate Cancer

• Registration Number: NCT02159690
• Lead Sponsor: Kenneth Pienta, MD

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 available

Study Timeline

• Study First Submitted: 2014-06-06
• Study First Submitted QC: 2014-06-06
• Study First Posted: 2014-06-10
• Study Start: 2014-09
• Status Verified: 2015-01
• Primary Completion: 2015-01
• Study Completion: 2015-01
• Last Update Submitted: 2015-01-22
• Last Update Posted: 2015-01-26

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Proportion of prostatectomy specimens with a complete response rate	12 weeks	Proportion of prostatectomy specimens with complete response rate after 12 weeks of therapy

Secondary Outcome Measures

Name	Time	Method
Proportion of radiographic disappearance of MRI detectable significant prostate nodules	12 weeks	Proportion of radiographic disappearance of MRI detectable significant prostate nodules after 12 weeks of therapy.
PSA progression free survival	2 years after last accrual	The biochemical (i.e. PSA) progression free survival estimate two years after the last patient has accrued.
Proportion of prostatectomy specimens with a negative surgical margin rate	12 weeks	Proportion of prostatectomy specimens with a negative surgical margin rate after 12 weeks of therapy
Proportion of prostatectomy specimens with pathologic T3 disease	12 weeks	Proportion of prostatectomy specimens with pathologic T3 disease after 12 weeks of therapy
Change in immunologic parameters (TREC levels and antibody responses)	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).
Exploratory biomarkers assessment	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.
Proportion of prostatectomy specimens with a near-pathologic complete response	12 weeks	Proportion of prostatectomy specimens with a near-pathologic complete response (\<=5mm of residual tumor) after 12 weeks of therapy
Incidence and severity of adverse events	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
Proportion of men who receive adjuvant radiation therapy within 1 year of prostatectomy	64 weeks	Proportion of men who receive adjuvant radiation therapy within 1 year of prostatectomy (12 weeks of therapy + 1 year = 64 weeks)
Overall survival	2 years after last accrual	The overall survival estimate two years after the last patient has accrued.

Trial Locations

Locations (1)

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States