Trial Outcomes & Findings for Apalutamide and Leuprolide in Intermediate and High-risk Prostate Cancer (NCT NCT02770391)
NCT ID: NCT02770391
Last Updated: 2022-06-21
Results Overview
To evaluate the differential effect of neo-adjuvant leuprolide and ARN-509 on dihydrotestosterone (DHT) concentration in benign prostate tissue based on HSD3B1 genotype.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
54 participants
Primary outcome timeframe
Up to 28 Days
Results posted on
2022-06-21
Participant Flow
Participant milestones
| Measure |
Apalutamide + Leuprolide Acetate
All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before
Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
Radical prostatectomy
|
|---|---|
|
Overall Study
STARTED
|
54
|
|
Overall Study
COMPLETED
|
48
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
Apalutamide + Leuprolide Acetate
All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before
Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
Radical prostatectomy
|
|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Surgery delayed unevaluable
|
2
|
|
Overall Study
Treatment discontinued due to treatment inturruption
|
1
|
Baseline Characteristics
Apalutamide and Leuprolide in Intermediate and High-risk Prostate Cancer
Baseline characteristics by cohort
| Measure |
Apalutamide + Leuprolide Acetate
n=54 Participants
All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before
Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
Radical prostatectomy
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
26 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
28 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
54 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
53 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
46 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 28 DaysPopulation: Participants with sufficient tissue each gave two samples
To evaluate the differential effect of neo-adjuvant leuprolide and ARN-509 on dihydrotestosterone (DHT) concentration in benign prostate tissue based on HSD3B1 genotype.
Outcome measures
| Measure |
Apalutamide + Leuprolide Acetate
n=30 Tissue Sample
All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before
Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
Radical prostatectomy
|
|---|---|
|
Dihydrotestosterone (DHT) Concentration in Benign Prostate Tissue After a Combination Drug Treatment Based on Genotype Status
homozygous (1245A)
|
9.066 nM
Standard Error 7.775
|
|
Dihydrotestosterone (DHT) Concentration in Benign Prostate Tissue After a Combination Drug Treatment Based on Genotype Status
heterozygous (1254C)
|
5.917 nM
Standard Error 3.458
|
|
Dihydrotestosterone (DHT) Concentration in Benign Prostate Tissue After a Combination Drug Treatment Based on Genotype Status
homozygous (1245C)
|
9.345 nM
Standard Error 5.607
|
PRIMARY outcome
Timeframe: Up to 28 DaysPopulation: Participants with sufficient tissue each gave two samples
To evaluate the differential effect of neo-adjuvant leuprolide and ARN-509 on dihydrotestosterone (DHT) concentration in malignant prostate tissue based on HSD3B1 genotype.
Outcome measures
| Measure |
Apalutamide + Leuprolide Acetate
n=48 Tissue Sample
All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before
Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
Radical prostatectomy
|
|---|---|
|
Dihydrotestosterone (DHT) Concentration in Malignant Prostate Tissue After a Combination Drug Treatment Based on Genotype Status
homozygous (1245A)
|
8.855 nM
Standard Error 7.4847
|
|
Dihydrotestosterone (DHT) Concentration in Malignant Prostate Tissue After a Combination Drug Treatment Based on Genotype Status
heterozygous (1254C)
|
5.238 nM
Standard Error 3.822
|
|
Dihydrotestosterone (DHT) Concentration in Malignant Prostate Tissue After a Combination Drug Treatment Based on Genotype Status
homozygous (1245C)
|
2.622 nM
Standard Error 1.530
|
SECONDARY outcome
Timeframe: Up to 28 DaysPopulation: Participants with sufficient tissue gave two samples
To evaluate the differential effect of neoadjuvant leuprolide and ARN-509 on other androgens (testosterone (T), dehydroepiandrosterone (DHEA), androstenediol, 5?-androstanedione (5?-dione), androstenedione (AD), androsterone and 5?-androstanediol) concentration in benign prostate tissue based on HSD3B1 genotype.
Outcome measures
| Measure |
Apalutamide + Leuprolide Acetate
n=30 Tissue Sample
All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before
Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
Radical prostatectomy
|
|---|---|
|
Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
DHT homozygous(1245A)
|
9.066 nM
Standard Error 7.775
|
|
Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
T homozygous(1245A)
|
6.901 nM
Standard Error 2.372
|
|
Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
DHEA homozygous(1245A)
|
46.110 nM
Standard Error 82.578
|
|
Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
AD homozygous(1245A)
|
8.394 nM
Standard Error 2.168
|
|
Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
DHT heterozygous
|
5.917 nM
Standard Error 3.458
|
|
Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
T heterozygous
|
4.929 nM
Standard Error 1.285
|
|
Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
DHEA heterozygous
|
18.5788 nM
Standard Error 13.02
|
|
Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
AD heterozygous
|
6.083 nM
Standard Error 2.5522
|
|
Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
DHT homozygous (1245C)
|
9.345 nM
Standard Error 5.607
|
|
Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
T homozygous (1245C)
|
4.704 nM
Standard Error 4.166
|
|
Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
AD homozygous (1245C)
|
8.303 nM
Standard Error 2.841
|
SECONDARY outcome
Timeframe: Up to 28 DaysPopulation: Participants with sufficient tissue gave two samples
To evaluate the effect of neoadjuvant ARN-509 on other androgens (DHT, T, DHEA, androstenediol, 5?-dione, AD, androsterone and 5?-androstanediol) concentration in malignant prostate tissue after neoadjuvant leuprolide and ARN-509.
Outcome measures
| Measure |
Apalutamide + Leuprolide Acetate
n=48 Tissue Sample
All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before
Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
Radical prostatectomy
|
|---|---|
|
Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
DHT homozygous (1245A)
|
8.855 nM
Standard Error 7.4847
|
|
Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
T homozygous (1245A)
|
5.691 nM
Standard Error 2.531
|
|
Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
DHEA homozygous (1245A)
|
22.941 nM
Standard Error 11.523
|
|
Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
AD homozygous (1245A)
|
7.974 nM
Standard Error 4.005
|
|
Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
DHT heterozygous
|
5.238 nM
Standard Error 3.822
|
|
Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
T heterozygous
|
5.719 nM
Standard Error 3.513
|
|
Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
DHEA heterozygous
|
24.543 nM
Standard Error 16.779
|
|
Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
AD heterozygous
|
8.593 nM
Standard Error 3.736
|
|
Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
DHT homozygous (1245C)
|
2.622 nM
Standard Error 1.530
|
|
Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
T homozygous (1245C)
|
4.489 nM
Standard Error 1.197
|
|
Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
DHEA homozygous (1245C)
|
1.421 nM
Standard Error 0
|
|
Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
AD homozygous (1245C)
|
6.959 nM
Standard Error 3.956
|
SECONDARY outcome
Timeframe: Up to 28 DaysPopulation: Insufficent Tissue
To compare the level of DHT, T, DHEA, androstenediol, 5alpha-dione, AD, androsterone and 5alpha-androstanediol between normal and malignant prostate tissue after neoadjuvant leuprolide and ARN-509.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 28 DaysPopulation: Participants with sufficient tissue for PSA and H3K27 were Analyzed. Two samples collected per participant. There was insufficient tissue for TMPRSS2, EZH2, H3K27, and UBE2C expression.
To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C tissue expression (via IHC) in malignant prostate tissue after treatment with Leuprolide and Apalutamide.
Outcome measures
| Measure |
Apalutamide + Leuprolide Acetate
n=78 Tissue Sample
All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before
Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
Radical prostatectomy
|
|---|---|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via IHC) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
PSA Homozygous (1245A)
|
1.15 nM
Standard Error 0.662
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via IHC) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
H3K27 Homozygous (1245A)
|
1.619 nM
Standard Error 0.882
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via IHC) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
PSA heterozygous
|
1.393 nM
Standard Error 0.786
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via IHC) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
H3K27 heterozygous
|
1.633 nM
Standard Error 0.890
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via IHC) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
PSA Homozygous (1245C)
|
1.375 nM
Standard Error 1.500
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via IHC) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
H3K27 Homozygous (1245C)
|
0.744 nM
Standard Error 0.756
|
SECONDARY outcome
Timeframe: Up to 28 DaysPopulation: Participants with sufficient tissue for PSA, FKBP5, TMPRSS2 were analyzed. Two samples were collected from each participant. There was insufficient tissues for the EZH2, H3K27, and UBE2C expression.
To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C tissue expression (via qPCR) in malignant prostate tissue after treatment with Leuprolide and Apalutamide.
Outcome measures
| Measure |
Apalutamide + Leuprolide Acetate
n=78 Tissue Sample
All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before
Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
Radical prostatectomy
|
|---|---|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
PSA homozygous (1245A)
|
1.474 nM
Standard Error 1.488
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
FKBP5 homozygous (1245A)
|
1.304 nM
Standard Error 0.874
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
TMPRSS2 homozygous (1245A)
|
1.603 nM
Standard Error 1.071
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
PSA heterozygous
|
1.127 nM
Standard Error 1.109
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
FKBP5 heterozygous
|
1.127 nM
Standard Error 1.109
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
TMPRSS2 heterozygous
|
1.742 nM
Standard Error 1.790
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
PSA homozygous (1245C)
|
2.221 nM
Standard Error 1.027
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
FKBP5 homozygous (1245C)
|
2.221 nM
Standard Error 1.027
|
|
PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
TMPRSS2 homozygous (1245C)
|
2.345 nM
Standard Error 1.145
|
SECONDARY outcome
Timeframe: Up to 28 DaysPopulation: Insufficient tissue
To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27 and UBE2C tissue expression (via IHC) in benign prostate tissue after treatment with Leuprolide and Apalutamide.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 28 DaysPopulation: Insufficient Tissue
To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27 and UBE2C tissue expression (via qPCR) in benign prostate tissue after treatment with Leuprolide and Apalutamide.
Outcome measures
Outcome data not reported
Adverse Events
Apalutamide + Leuprolide Acetate
Serious events: 1 serious events
Other events: 47 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Apalutamide + Leuprolide Acetate
n=54 participants at risk
All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before
Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
Radical prostatectomy
|
|---|---|
|
Reproductive system and breast disorders
Genital Edema
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
Other adverse events
| Measure |
Apalutamide + Leuprolide Acetate
n=54 participants at risk
All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before
Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
Radical prostatectomy
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
5.6%
3/54 • Up to 8 Weeks following the last dose of study drug
|
|
Endocrine disorders
Hypothyroidism
|
16.7%
9/54 • Up to 8 Weeks following the last dose of study drug
|
|
Eye disorders
Eye disorders - Other, specify (Intermittent dry & watering eyes)
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Gastrointestinal disorders
Bloating
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Gastrointestinal disorders
Constipation
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Gastrointestinal disorders
Diarrhea
|
9.3%
5/54 • Up to 8 Weeks following the last dose of study drug
|
|
Gastrointestinal disorders
Dry mouth
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Gastrointestinal disorders
Nausea
|
7.4%
4/54 • Up to 8 Weeks following the last dose of study drug
|
|
General disorders
Edema, face
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
General disorders
Facial pain
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
General disorders
Fatigue
|
53.7%
29/54 • Up to 8 Weeks following the last dose of study drug
|
|
General disorders
Localized edema
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Infections and infestations
Upper respiratory infection
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Investigations
Alanine aminotransferase increased
|
9.3%
5/54 • Up to 8 Weeks following the last dose of study drug
|
|
Investigations
Aspartate aminotransferase increased
|
11.1%
6/54 • Up to 8 Weeks following the last dose of study drug
|
|
Investigations
Creatinine Increased
|
7.4%
4/54 • Up to 8 Weeks following the last dose of study drug
|
|
Investigations
Hyperglycemia
|
9.3%
5/54 • Up to 8 Weeks following the last dose of study drug
|
|
Investigations
Hyperkalemia
|
7.4%
4/54 • Up to 8 Weeks following the last dose of study drug
|
|
Investigations
Hypernatremia
|
5.6%
3/54 • Up to 8 Weeks following the last dose of study drug
|
|
Investigations
Hypoalbuminemia
|
3.7%
2/54 • Up to 8 Weeks following the last dose of study drug
|
|
Investigations
Hyponatremia
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Investigations
Lymphocyte Count Decreased
|
9.3%
5/54 • Up to 8 Weeks following the last dose of study drug
|
|
Investigations
Platelet count decreased
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Investigations
Weight Loss
|
3.7%
2/54 • Up to 8 Weeks following the last dose of study drug
|
|
Investigations
White blood cell decreased
|
5.6%
3/54 • Up to 8 Weeks following the last dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.0%
7/54 • Up to 8 Weeks following the last dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
3.7%
2/54 • Up to 8 Weeks following the last dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.7%
2/54 • Up to 8 Weeks following the last dose of study drug
|
|
Nervous system disorders
Cognitive Disturbance
|
5.6%
3/54 • Up to 8 Weeks following the last dose of study drug
|
|
Nervous system disorders
Cognitive Impairment
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Nervous system disorders
Dizziness
|
11.1%
6/54 • Up to 8 Weeks following the last dose of study drug
|
|
Nervous system disorders
Dysgeusia
|
14.8%
8/54 • Up to 8 Weeks following the last dose of study drug
|
|
Nervous system disorders
Headache
|
16.7%
9/54 • Up to 8 Weeks following the last dose of study drug
|
|
Nervous system disorders
Nervous system disorders - Other, specify (Restless leg syndrome (6); Mental fogginess (2))
|
14.8%
8/54 • Up to 8 Weeks following the last dose of study drug
|
|
Nervous system disorders
Paresthesia
|
3.7%
2/54 • Up to 8 Weeks following the last dose of study drug
|
|
Psychiatric disorders
Agitation
|
3.7%
2/54 • Up to 8 Weeks following the last dose of study drug
|
|
Psychiatric disorders
Anxiety
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Psychiatric disorders
Depression
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Psychiatric disorders
Insomnia
|
14.8%
8/54 • Up to 8 Weeks following the last dose of study drug
|
|
Psychiatric disorders
Libido decrease
|
5.6%
3/54 • Up to 8 Weeks following the last dose of study drug
|
|
Psychiatric disorders
Psychiatric disorders - Other, specify (Flat affect)
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Psychiatric disorders
Restlessness
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Renal and urinary disorders
Dysuria
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Renal and urinary disorders
Urinary Frequency
|
7.4%
4/54 • Up to 8 Weeks following the last dose of study drug
|
|
Renal and urinary disorders
Urinary Retention
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Reproductive system and breast disorders
Breast Pain
|
3.7%
2/54 • Up to 8 Weeks following the last dose of study drug
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Reproductive system and breast disorders
Prostatic obstruction
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders - Other, specify (Penis shrinkage)
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.6%
3/54 • Up to 8 Weeks following the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
11.1%
6/54 • Up to 8 Weeks following the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
9.3%
5/54 • Up to 8 Weeks following the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify (Skin disorder (2))
|
3.7%
2/54 • Up to 8 Weeks following the last dose of study drug
|
|
Vascular disorders
Hot Flashes
|
51.9%
28/54 • Up to 8 Weeks following the last dose of study drug
|
|
Vascular disorders
Hypertension
|
7.4%
4/54 • Up to 8 Weeks following the last dose of study drug
|
|
Vascular disorders
Hypotension
|
1.9%
1/54 • Up to 8 Weeks following the last dose of study drug
|
Additional Information
Moshe Ornstein,
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Phone: 18662238100
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place