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

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT02849990
• Collaborator: Janssen Scientific Affairs, LLC (Industry), National Cancer Institute (NCI) (NIH)
• Enrollment: 22
• Location: 1
• Arm: 1
• Actual Duration (Months): 45.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stage III Prostate Adenocarcinoma AJCC v7; Stage III Prostate Cancer AJCC v7; Stage IV Prostate Adenocarcinoma AJCC v7; Stage IV Prostate Cancer AJCC v7	Drug: Abiraterone Acetate; Drug: Apalutamide; Drug: Degarelix; Drug: Indomethacin; Other: Laboratory Biomarker Analysis; Drug: Prednisone	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. The rate of the pathologic complete response (pCR) (i.e. no evidence of residual tumor) as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin.

SECONDARY OBJECTIVES:

1. To determine the negative margin rate as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin.

2. To determine the rate of near pCR (i.e. =< 5 mm of residual tumor) as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin.

3. To determine the rate of pathologic T3 disease as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin.

4. To determine the rate of nodal metastases as assessed on surgical lymph node specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin.

5. To determine the apoptotic index (i.e. percentage of tumor cells undergoing apoptosis) as determined by cleaved caspase-3 immunohistochemistry following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin.

6. To determine the proportion of men who receive adjuvant radiation therapy within 1-year of prostatectomy.

7. To determine the biochemical (i.e. prostate-specific antigen [PSA]) progression free survival estimate two years after the last patient has accrued (i.e. confirmed PSA post-radical prostatectomy >= 0.2 ng/mL).

8. To determine the overall survival estimate two years after the last patient has accrued.

9. 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.

10. Exploratory biomarker assessment.

OUTLINE:

Patients receive apalutamide and abiraterone acetate orally (PO) daily, prednisone PO twice per day (BID) and indomethacin PO three times per day (TID). Patients also receive degarelix subcutaneously (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.

After completion of study treatment, patients are followed up at 28, 113, 450 and 815 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Neoadjuvant Study of Apalutamide, Abiraterone Acetate, Prednisone, Degarelix and Indomethacin in Men With Localized Prostate Cancer Pre-Prostatectomy
• Actual Study Start Date: Mar 9, 2017
• Actual Primary Completion Date: Dec 10, 2018
• Actual Study Completion Date: Dec 10, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (neoadjuvant chemotherapy) 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; Given PO; Other Names: CB7630 Zytiga ; Drug: Apalutamide; Given PO; Other Names: ARN 509 ARN-509 ARN509 JNJ 56021927 JNJ-56021927 ; Drug: Degarelix; Given SC; Other Names: FE200486 Firmagon ; Drug: Indomethacin; Given PO; Other Names: Indocin Indometacin ; Other: Laboratory Biomarker Analysis; Correlative study; Drug: Prednisone; Given PO; Other Names: .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

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response Rate as Assessed From Prostatectomy Specimens Following Neoadjuvant Treatment [At 3 months]

   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.

Secondary Outcome Measures

1. Apoptotic Index (i.e. Percentage of Tumor Cells Undergoing Apoptosis) [At 3 months]

   Will be determined by cleaved caspase-3 immunohistochemistry.

2. Number of Patients With a Negative Margin After 3 Months of Treatment [At 3 months]

   The absence of tumor cells at the prostate margin will be assessed using standard pathological practices on prostatectomy specimens (i.e. after 3 months of treatment).

3. Overall Survival (OS) [At 2 years]

   Will will report the number of participants alive at 2-years following enrollment.

4. Number of Patients With a Near Pathologic Complete Response After 3 Months of Treatment [At 3 months]

   The near pathologic complete response will be defined as =< 5 mm of residual tumor as assessed on prostatectomy specimens after 3 months of treatment.

5. Number of Patients With no Nodal Metastases After 3 Months of Treatment. [At 3 months]

   The presence of tumor cells within surgically excised lymph nodes will be assessed after 3 months of treament.

6. Number of Patients With Pathologic T3 Disease After 3 Months of Treatment. [At 3 months]

   The presence of T3 disease (e.g. extraprostatic tumor not invading adjacent structures) will be determine from the prostatectomy specimen after 3 months of treament.

7. Number of Participants Without Biochemical Failure at 2 Years [At 2 years]

   Prostate-specific antigen progression (i.e. biochemical failure) will be defined per the American Urological Association guidelines (i.e. confirmed prostate-specific antigen post-radical prostatectomy >= 0.2 ng/mL). We will report the number of patients without biochemical failure at 2 years.

8. The Proportion of Men Who Receive Adjuvant Radiation Therapy [Up to 1 year post prostatectomy]

   Patients that received radiation following prostatetomy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >= 2.5 x ULN; Note: in subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible

• Abnormal kidney function (glomerular filtration rate GFR < 45 mL/min)

• Serum albumin < 3 g/dL

• Serum potassium < 3.5 mmol/L

• Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)

• Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization

• History of stroke within the last 5-years

• History of gastrointestinal (GI) bleed requiring transfusion

• History of peptic ulcer disease requiring treatment within the last 5-years

• History of asthma that is nonsteroidal anti-inflammatory drug (NSAID)-induced or with asthma that is classified as 'mild-persistent' or worse (based on symptoms occurring more than 2 days per week)

• Uncontrolled hypertension

• Gastrointestinal disorder affecting absorption

• Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)

• Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/ prednisolone once daily

• Any condition that in the opinion of the investigator, would preclude participation in this study

• Child Pugh class B & C

• Pre-existing viral hepatitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Michael Schweizer, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 23, 2018

More Information

Publications

None provided.

• Responsible Party: Michael Schweizer, Associate Professor, Division of Medical Oncology, University of Washington
• ClinicalTrials.gov Identifier: NCT02849990
• Other Study ID Numbers: 9628; NCI-2016-01027; 9628; P30CA015704; RG1716056
• First Posted: Jul 29, 2016
• Last Update Posted: Jan 13, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms; Adenocarcinoma; Prednisone; Cortisone; Indomethacin; Abiraterone Acetate

Study Results

Participant Flow

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy)
Arm/Group Description	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Period Title: Overall Study
STARTED	22
COMPLETED	20
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy)
Arm/Group Description	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Overall Participants	20
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	20 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	1 5%
Black or African American	1 5%
White	18 90%
More than one race	0 0%
Unknown or Not Reported	0 0%
Prostate Specific Antigen (PSA) (ng/mL) [Median (Full Range) ]
Median (Full Range) [ng/mL]	10
Total Gleason score (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	9

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response Rate as Assessed From Prostatectomy Specimens Following Neoadjuvant Treatment
Description	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.
Time Frame	At 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy)
Arm/Group Description	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Measure Participants	20
Count of Participants [Participants]	1 5%

2. Secondary Outcome

Title	Apoptotic Index (i.e. Percentage of Tumor Cells Undergoing Apoptosis)
Description	Will be determined by cleaved caspase-3 immunohistochemistry.
Time Frame	At 3 months

Outcome Measure Data

Analysis Population Description

Due to limited post-treatment tumor tissue, assessment of apoptotic index is not feasible.

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy)
Arm/Group Description	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Measure Participants	0

3. Secondary Outcome

Title	Number of Patients With a Negative Margin After 3 Months of Treatment
Description	The absence of tumor cells at the prostate margin will be assessed using standard pathological practices on prostatectomy specimens (i.e. after 3 months of treatment).
Time Frame	At 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy)
Arm/Group Description	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Measure Participants	20
Negative margins	13 65%
Positive margins	7 35%

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Will will report the number of participants alive at 2-years following enrollment.
Time Frame	At 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy)
Arm/Group Description	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Measure Participants	20
Count of Participants [Participants]	20 100%

5. Secondary Outcome

Title	Number of Patients With a Near Pathologic Complete Response After 3 Months of Treatment
Description	The near pathologic complete response will be defined as =< 5 mm of residual tumor as assessed on prostatectomy specimens after 3 months of treatment.
Time Frame	At 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy)
Arm/Group Description	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Measure Participants	20
Count of Participants [Participants]	6 30%

6. Secondary Outcome

Title	Number of Patients With no Nodal Metastases After 3 Months of Treatment.
Description	The presence of tumor cells within surgically excised lymph nodes will be assessed after 3 months of treament.
Time Frame	At 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy)
Arm/Group Description	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Measure Participants	20
No nodal metastases	13 65%
Nodal metastases	7 35%

7. Secondary Outcome

Title	Number of Patients With Pathologic T3 Disease After 3 Months of Treatment.
Description	The presence of T3 disease (e.g. extraprostatic tumor not invading adjacent structures) will be determine from the prostatectomy specimen after 3 months of treament.
Time Frame	At 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy)
Arm/Group Description	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Measure Participants	20
Count of Participants [Participants]	18 90%

8. Secondary Outcome

Title	Number of Participants Without Biochemical Failure at 2 Years
Description	Prostate-specific antigen progression (i.e. biochemical failure) will be defined per the American Urological Association guidelines (i.e. confirmed prostate-specific antigen post-radical prostatectomy >= 0.2 ng/mL). We will report the number of patients without biochemical failure at 2 years.
Time Frame	At 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy)
Arm/Group Description	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Measure Participants	20
Number [participants]	18 90%

9. Secondary Outcome

Title	The Proportion of Men Who Receive Adjuvant Radiation Therapy
Description	Patients that received radiation following prostatetomy
Time Frame	Up to 1 year post prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy)
Arm/Group Description	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Measure Participants	20
Count of Participants [Participants]	7 35%

Adverse Events

Time Frame	Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
Arm/Group Title	Treatment (Neoadjuvant Chemotherapy)
Arm/Group Description	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
All Cause Mortality
	Treatment (Neoadjuvant Chemotherapy)
	Affected / at Risk (%)	# Events
Total	0/22 (0%)
Serious Adverse Events
	Treatment (Neoadjuvant Chemotherapy)
	Affected / at Risk (%)	# Events
Total	0/22 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Neoadjuvant Chemotherapy)
	Affected / at Risk (%)	# Events
Total	22/22 (100%)
Blood and lymphatic system disorders
Epistaxis	3/22 (13.6%)
Endocrine disorders
Hot flashes	18/22 (81.8%)
General disorders
Fatigue	16/22 (72.7%)
Mood change	5/22 (22.7%)
Insomnia	3/22 (13.6%)
Dizziness	2/22 (9.1%)
Gastrointestinal disorder	11/22 (50%)
Hepatobiliary disorders
Transaminitis	4/22 (18.2%)
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder	6/22 (27.3%)
Nervous system disorders
Cognitive Changes	11/22 (50%)
Headaches	2/22 (9.1%)
Balance Problem	2/22 (9.1%)
Skin and subcutaneous tissue disorders
Injection site reaction	3/22 (13.6%)
Vascular disorders
Hypertension	9/22 (40.9%)
Hypotension	2/22 (9.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.