Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

Reproductive Control Agents

All Drugs and Chemicals

Leuprolide

Antineoplastic Agents, Hormonal

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, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3

Leuprolide acetate

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.

Apalutamide

Radical prostatectomy

Moshe Ornstein, MD

This is a research study to test an investigational drug (Not FDA approved), Apalutamide given in combination with Leuprolide acetate (FDA approved) in men diagnosed with high-risk prostate cancer who have already selected to have surgery to remove their prostate gland as part of their treatment plan. The main purpose of this study is to determine how tumors make androgens (male hormones), which makes these tumors more aggressive and resistant to hormonal therapy and how a short period of treatment with Apalutamide and leuprolide acetate prior to surgery can affect the production of these hormones in normal and malignant prostate tissue.

Primary Objective: To evaluate the differential effect of neo-adjuvant leuprolide and Apalutamide on dihydrotestosterone (DHT) concentration in benign prostate tissue based on HSD3B1 genotype.

Secondary Objective(s): To evaluate the differential effect of neoadjuvant leuprolide and Apalutamide on other androgen (testosterone (T), dehydroepiandrosterone (DHEA), androstenediol, 5α-androstanedione (5α-dione), androstenedione (AD), androsterone and 5α-androstanediol) concentrations in benign and malignant prostate tissue based on HSD3B1 genotype.

To compare the level of DHT, T, DHEA, androstenediol, 5α-dione, AD, androsterone and 5α-androstanediol between normal and malignant prostate tissue after neoadjuvant treatment with leuprolide and Apalutamide

To determine the safety of the combination of Leuprolide and Apalutamide administered prior to radical prostatectomy

To evaluate prostatic specific antigen (PSA), FKBP5, TMPRSS2, EZH2, H3K27 and UBE2C tissue expression (via immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR)) in benign and malignant prostate tissue after treatment with Leuprolide and Apalutamide.

Apalutamide and Leuprolide in Intermediate and High-risk Prostate Cancer

The Association Between HSD3B1 Genotype and Steroid Metabolism in Normal and Prostate Cancer Tissue of Men With Intermediate and High-risk Prostate Cancer Undergoing Radical Prostatectomy After Treatment With Apalutamide and Leuprolide

To evaluate the differential effect of neo-adjuvant leuprolide and ARN-509 on dihydrotestosterone (DHT) concentration in benign prostate tissue based on HSD3B1 genotype.

To evaluate the differential effect of neo-adjuvant leuprolide and ARN-509 on dihydrotestosterone (DHT) concentration in malignant prostate tissue based on HSD3B1 genotype.

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.

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.

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.

To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C tissue expression (via IHC) in malignant prostate tissue after treatment with Leuprolide and Apalutamide.

To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C tissue expression (via qPCR) in malignant prostate tissue after treatment with Leuprolide and Apalutamide.

To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27 and UBE2C tissue expression (via IHC) in benign prostate tissue after treatment with Leuprolide and Apalutamide.

To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27 and UBE2C tissue expression (via qPCR) in benign prostate tissue after treatment with Leuprolide and Apalutamide.

Case Comprehensive Cancer Center

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

Apalutamide + Leuprolide Acetate

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Moshe Ornstein,

homozygous (1245A)

heterozygous (1254C)

homozygous (1245C)

Participants with sufficient tissue each gave two samples

Dihydrotestosterone (DHT) Concentration in Benign Prostate Tissue After a Combination Drug Treatment Based on Genotype Status

DHT homozygous(1245A)

T homozygous(1245A)

DHEA homozygous(1245A)

AD homozygous(1245A)

DHT heterozygous

T heterozygous

DHEA heterozygous

AD heterozygous

DHT homozygous (1245C)

T homozygous (1245C)

AD homozygous (1245C)

Participants with sufficient tissue gave two samples

Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.

DHT homozygous (1245A)

T homozygous (1245A)

DHEA homozygous (1245A)

AD homozygous (1245A)

DHEA homozygous (1245C)

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.

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.

PSA Homozygous (1245A)

H3K27 Homozygous (1245A)

PSA heterozygous

H3K27 heterozygous

PSA Homozygous (1245C)

H3K27 Homozygous (1245C)

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.

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)

FKBP5 homozygous (1245A)

TMPRSS2 homozygous (1245A)

FKBP5 heterozygous

TMPRSS2 heterozygous

PSA homozygous (1245C)

FKBP5 homozygous (1245C)

TMPRSS2 homozygous (1245C)

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.

PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.

PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via IHC) in Benign Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.

PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Benign Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.

Spots Global Cancer Trial Database for hsd3b1 genotype