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

NCT02159690 | Withdrawn Phase 2

• 1 other identifier: Neoadj enz/abi/dut/deg
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer; Localized Prostate Cancer

Keywords

prostate cancer; prostatectomy; localized prostate cancer

Outcome Measures

Primary Outcomes (1)

• Proportion of prostatectomy specimens with a complete response rate

  Proportion of prostatectomy specimens with complete response rate after 12 weeks of therapy

  12 weeks

Secondary Outcomes (10)

• Proportion of prostatectomy specimens with a negative surgical margin rate

  12 weeks

• Proportion of prostatectomy specimens with a near-pathologic complete response

  12 weeks

• Proportion of prostatectomy specimens with pathologic T3 disease

  12 weeks

• Change in immunologic parameters (TREC levels and antibody responses)

  16 weeks

• Proportion of radiographic disappearance of MRI detectable significant prostate nodules

  12 weeks

Interventions

Enzalutamide DRUG

160mg

Also known as: MDV3100, Xtandi

Abiraterone acetate DRUG

1000mg

Also known as: Zytiga

Prednisone DRUG

5mg twice daily (to blunt mineralocorticoid side effects from abiraterone)

Also known as: Deltasone

Dutasteride DRUG

0.5mg

Also known as: Avodart

Degarelix DRUG

240mg SC loading dose on day 1, then three 80mg SC injections every 4 weeks thereafter

Also known as: Firmagon

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kenneth Pienta, MD: lead
• Prostate Cancer Foundation Norway: collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; Abiraterone Acetate; Prednisone; Dutasteride; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Azasteroids; Steroids, Heterocyclic

Study Officials

• Kenneth J Pienta, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 6, 2014
• First Posted: June 10, 2014
• Study Start: September 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: January 26, 2015

Record last verified: 2015-01

Locations

US (1)