Trial Outcomes & Findings for A Phase II Neoadjuvant Study of Apalutamide, Abiraterone Acetate, Prednisone, Degarelix and Indomethacin in Men With Localized Prostate Cancer Pre-prostatectomy (NCT NCT02849990)

Last Updated: 2022-01-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

At 3 months

Results posted on

2022-01-13

Participant Flow

Participant milestones

Participant milestones
Measure	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Overall Study STARTED	22
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Abiraterone Acetate: Given PO Apalutamide: Given PO Degarelix: Given SC Indomethacin: Given PO Laboratory Biomarker Analysis: Correlative study Prednisone: Given PO
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Neoadjuvant Chemotherapy) n=20 Participants 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
Age, Customized	63 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Prostate Specific Antigen (PSA)	10 ng/mL n=5 Participants
Total Gleason score	9 units on a scale n=5 Participants

PRIMARY outcome

Timeframe: At 3 months

Outcome measures

Outcome measures
Measure	Treatment (Neoadjuvant Chemotherapy) n=20 Participants 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
Pathologic Complete Response Rate as Assessed From Prostatectomy Specimens Following Neoadjuvant Treatment	1 Participants

SECONDARY outcome

Timeframe: At 3 months

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

Will be determined by cleaved caspase-3 immunohistochemistry.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Treatment (Neoadjuvant Chemotherapy) n=20 Participants 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
Number of Patients With a Negative Margin After 3 Months of Treatment Negative margins	13 Participants
Number of Patients With a Negative Margin After 3 Months of Treatment Positive margins	7 Participants

SECONDARY outcome

Timeframe: At 2 years

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

Outcome measures

Outcome measures
Measure	Treatment (Neoadjuvant Chemotherapy) n=20 Participants 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 Survival (OS)	20 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment (Neoadjuvant Chemotherapy) n=20 Participants 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
Number of Patients With a Near Pathologic Complete Response After 3 Months of Treatment	6 Participants

SECONDARY outcome

Timeframe: At 3 months

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

Outcome measures

Outcome measures
Measure	Treatment (Neoadjuvant Chemotherapy) n=20 Participants 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
Number of Patients With no Nodal Metastases After 3 Months of Treatment. No nodal metastases	13 Participants
Number of Patients With no Nodal Metastases After 3 Months of Treatment. Nodal metastases	7 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment (Neoadjuvant Chemotherapy) n=20 Participants 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
Number of Patients With Pathologic T3 Disease After 3 Months of Treatment.	18 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment (Neoadjuvant Chemotherapy) n=20 Participants 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
Number of Participants Without Biochemical Failure at 2 Years	18 participants

SECONDARY outcome

Timeframe: Up to 1 year post prostatectomy

Patients that received radiation following prostatetomy

Outcome measures

Outcome measures
Measure	Treatment (Neoadjuvant Chemotherapy) n=20 Participants 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
The Proportion of Men Who Receive Adjuvant Radiation Therapy	7 Participants

Adverse Events

Treatment (Neoadjuvant Chemotherapy)

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Treatment (Neoadjuvant Chemotherapy) n=22 participants at risk 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
General disorders Fatigue	72.7% 16/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
General disorders Mood change	22.7% 5/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
General disorders Insomnia	13.6% 3/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
General disorders Dizziness	9.1% 2/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	27.3% 6/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
Nervous system disorders Cognitive Changes	50.0% 11/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
Nervous system disorders Headaches	9.1% 2/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
Nervous system disorders Balance Problem	9.1% 2/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
Endocrine disorders Hot flashes	81.8% 18/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
General disorders Gastrointestinal disorder	50.0% 11/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
Hepatobiliary disorders Transaminitis	18.2% 4/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
Skin and subcutaneous tissue disorders Injection site reaction	13.6% 3/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
Blood and lymphatic system disorders Epistaxis	13.6% 3/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
Vascular disorders Hypertension	40.9% 9/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.
Vascular disorders Hypotension	9.1% 2/22 • Adverse events were assessed for 30 days from the last dose of study drugs. All-cause mortality was assessed up to 2 years.

Additional Information

Dr. Michael Schweizer

University of Washington

Phone: 2066066252

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60