Clinical trial NCT02159690: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Prostate Cancer
Localized Prostate Cancer
Keywords: prostate cancer
prostatectomy
localized prostate cancer
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Prostate Cancer Foundation Norway
First posted: 2014-06-10
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of prostatectomy specimens with a complete response rate
timeFrame: 12 weeks
Secondary outcomes:
measure: Proportion of prostatectomy specimens with a negative surgical margin rate
timeFrame: 12 weeks
measure: Proportion of prostatectomy specimens with a near-pathologic complete response
timeFrame: 12 weeks
measure: Proportion of prostatectomy specimens with pathologic T3 disease
timeFrame: 12 weeks
measure: Change in immunologic parameters (TREC levels and antibody responses)
timeFrame: 16 weeks
measure: Proportion of radiographic disappearance of MRI detectable significant prostate nodules
timeFrame: 12 weeks
measure: Proportion of men who receive adjuvant radiation therapy within 1 year of prostatectomy
timeFrame: 64 weeks
measure: PSA progression free survival
timeFrame: 2 years after last accrual
measure: Overall survival
timeFrame: 2 years after last accrual
measure: Incidence and severity of adverse events
timeFrame: 16 weeks
measure: Exploratory biomarkers assessment
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Kenneth J Pienta, MD
role: PRINCIPAL_INVESTIGATOR
References: