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

NCT02849990 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: 9628NCI-2016-01027P30CA015704RG1716056
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well apalutamide, abiraterone acetate, prednisone, degarelix, and indomethacin work in treating patients with prostate cancer that has spread from where it started to nearby tissue or lymph nodes before surgery. Androgen can cause the growth of tumor cells. Hormone therapy using apalutamide, abiraterone acetate, prednisone, degarelix, and indomethacin may fight prostate cancer by lowering the amount of androgen the body makes and/or blocking the use of androgen by the tumor cells.

Conditions

Stage III Prostate Adenocarcinoma AJCC v7; Stage III Prostate Cancer AJCC v7; Stage IV Prostate Adenocarcinoma AJCC v7; Stage IV Prostate Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response Rate as Assessed From Prostatectomy Specimens Following Neoadjuvant Treatment

  Pathologic complete response is defined as no evidence of cancer on fully submitted prostatectomy specimens using standard surgical pathology assessments (i.e. H\&E assessment will be used for the purpose of defining pathologic complete response per protocol) at 3 months.

  At 3 months

Secondary Outcomes (8)

• Apoptotic Index (i.e. Percentage of Tumor Cells Undergoing Apoptosis)

  At 3 months

• Number of Patients With a Negative Margin After 3 Months of Treatment

  At 3 months

• Overall Survival (OS)

  At 2 years

• Number of Patients With a Near Pathologic Complete Response After 3 Months of Treatment

  At 3 months

• Number of Patients With no Nodal Metastases After 3 Months of Treatment.

  At 3 months

Study Arms (1)

Treatment (neoadjuvant chemotherapy)

EXPERIMENTAL

Patients receive androgen receptor antagonist ARN-509 and abiraterone acetate PO daily, prednisone PO BID and indomethacin PO TID. Patients also receive degarelix SC on day 1 and every 4 weeks for 3 doses. Treatment continues for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo prostatectomy on day 85.

Drug: Abiraterone Acetate; Drug: Apalutamide; Drug: Degarelix; Drug: Indomethacin; Other: Laboratory Biomarker Analysis; Drug: Prednisone

Interventions

Abiraterone Acetate DRUG

Given PO

Also known as: CB7630, Zytiga

Treatment (neoadjuvant chemotherapy)

Apalutamide DRUG

Given PO

Also known as: ARN 509, ARN-509, ARN509, JNJ 56021927, JNJ-56021927

Treatment (neoadjuvant chemotherapy)

Degarelix DRUG

Given SC

Also known as: FE200486, Firmagon

Treatment (neoadjuvant chemotherapy)

Indomethacin DRUG

Given PO

Also known as: Indocin, Indometacin

Treatment (neoadjuvant chemotherapy)

Laboratory Biomarker Analysis OTHER

Correlative study

Treatment (neoadjuvant chemotherapy)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisonum, Prednitone, Promifen, Servisone, SK-Prednisone

Treatment (neoadjuvant chemotherapy)

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
• Eastern Cooperative Oncology 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 National Comprehensive Cancer Network \[NCCN\] 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
• 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)
• Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug; must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug
• Medications known to lower the seizure threshold (see list under prohibited meds) must be discontinued or substituted at least 4 weeks prior to study entry

You may not qualify if:

• Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)
• Prior use of apalutamide, abiraterone acetate or degarelix
• Prior or ongoing systemic therapy for prostate cancer including, but not limited to:
• Hormonal therapy (for example \[e.g.\] leuprolide, goserelin, triptorelin, degarelix)
• Cytochrome P450 (CYP)-17 inhibitors (e.g. ketoconazole)
• Antiandrogens (e.g. bicalutamide, nilutamide)
• Second generation antiandrogens (e.g. enzalutamide, apalutamide)
• 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
• Absolute neutrophil count \[ANC\] \< 1500/mm\^3
• Platelet count \< 100,000/mm\^3
• Hemoglobin \< 9 g/dL
• Total bilirubin \> 1.5 x upper limit of normal (ULN)

Sponsors & Collaborators

• University of Washington: lead
• Janssen Scientific Affairs, LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; apalutamide; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Indomethacin; Prednisone; deltacortene; prednylidene

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; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Results Point of Contact

• Title: Dr. Michael Schweizer
• Organization: University of Washington

schweize@uw.edu

2066066252

Study Officials

• Michael Schweizer

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Division of Medical Oncology

Study Record Dates

• First Submitted: July 25, 2016
• First Posted: July 29, 2016
• Study Start: March 9, 2017
• Primary Completion: December 10, 2018
• Study Completion: December 10, 2020
• Last Updated: January 13, 2022
• Results First Posted: January 18, 2020

Record last verified: 2021-12

Locations

US (1)