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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02159690
• Other study ID #: Neoadj enz/abi/dut/deg
• Status: Withdrawn
• Phase: Phase 2
• First received: June 6, 2014
• Last updated: January 22, 2015
• Start date: September 2014
• Est. completion date: January 2015

Study information

• Verified date: January 2015
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Localized Prostate Cancer
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Enzalutamide
160mg
• Abiraterone acetate
1000mg
• Prednisone
5mg twice daily (to blunt mineralocorticoid side effects from abiraterone)
• Dutasteride
0.5mg
• Degarelix
240mg SC loading dose on day 1, then three 80mg SC injections every 4 weeks thereafter

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Kenneth Pienta, MD	Prostate Cancer Foundation Norway

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of prostatectomy specimens with a complete response rate	Proportion of prostatectomy specimens with complete response rate after 12 weeks of therapy	12 weeks	No
Secondary	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	12 weeks	No
Secondary	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	12 weeks	No
Secondary	Proportion of prostatectomy specimens with pathologic T3 disease	Proportion of prostatectomy specimens with pathologic T3 disease after 12 weeks of therapy	12 weeks	No
Secondary	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).	16 weeks	No
Secondary	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.	12 weeks	No
Secondary	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)	64 weeks	No
Secondary	PSA progression free survival	The biochemical (i.e. PSA) progression free survival estimate two years after the last patient has accrued.	2 years after last accrual	No
Secondary	Overall survival	The overall survival estimate two years after the last patient has accrued.	2 years after last accrual	No
Secondary	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	16 weeks	Yes
Secondary	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.	16 weeks	No