Neoadjuvant Androgen Deprivation Therapy Plus Abiraterone With or Without Apalutamide for High-Risk Prostate Cancer

Study Overview
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Brief Summary
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This is a randomized study to evaluate the efficacy and safety neoadjuvant androgen deprivation therapy with goserelin and abiraterone with or without apalutamide prior to radical prostatectomy for patients diagnosed with localized high-risk prostate cancer.

Detailed Description
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In the prostate specific antigen (PSA) era, about 15% to 20% of patients are diagnosed with high-risk localized disease and radical prostatectomy is a standard therapy for this subgroup of patients. However, despite best local therapy, about 30-60% of high-risk patients will eventually develop biochemical relapse and a significant proportion of these patients may progress with metastatic disease and die from prostate cancer. Currently, there is no data supporting the use of neoadjuvant therapy for patients with high-risk disease since studies failed to demonstrate clinically significant benefit with standard androgen deprivation therapy (ADT). Following improved outcomes in other malignancies with the use of neoadjuvant therapy with active drugs in the metastatic setting, there is a growing interest in evaluating new-generation androgen receptor (AR)-targeted therapy in earlier stages of prostate cancer. Therefore, the goal of this study is to evaluate the efficacy and safety of neoadjuvant therapy with ADT and abiraterone versus maximal androgen blockade using ADT, abiraterone and apalutamide for patients with high-risk localized prostate cancer.

Official Title
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Phase II Study of Neoadjuvant Androgen Deprivation Therapy Plus Abiraterone With or Without Apalutamide for Patients With High-Risk Localized Prostate Cancer Prior to Radical Prostatectomy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Goserelin
* Drug: Prednisone
* Drug: Abiraterone
* Drug: Apalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic confirmed prostatic adenocarcinoma Non-castrate levels of testosterone (> 150 ng/dL) High-risk localized prostate cancer, defined by either: Tumor stage T3 by digital rectal examination, or Primary tumor Gleason score ≥ 8, or PSA ≥ 20 ng/mL Willing to undergo prostatectomy as primary treatment for localized prostate cancer Adequate hematologic, renal and hepatic function: WBC > 3000/uL Platelets > 150,000/uL Creatinine < 2 mg/dL Bilirubin < 1.5 x upper limit of normal (ULN) AST/ALT < 2 x ULN Karnofsky Performance Status (KPS) ≥ 80% Able to swallow the study drugs whole as tablets Exclusion Criteria: Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate Current or prior hormonal therapy, radiation therapy or chemotherapy for prostate cancer Evidence of metastatic disease (M1) on imaging studies Other prior malignancy less than or equal to 5 years prior to randomization with the exception of squamous or basal cell skin carcinoma Abnormal cardiac function as manifested by NYHA (New York Heart Association) class III or IV heart failure History of prior cardiac arrhythmia. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADT and Abiraterone<br>Goserelin 10.8 mg, single dose, subcutaneously. Abiraterone 1,000 mg, once daily, orally for 3 months. Prednisone 5 mg, once daily, orally for 3 months. | Drug: Goserelin<br>* Androgen Deprivation Therapy<br>* Other names: ADT;Drug: Prednisone<br>* Corticosteroid<br>Drug: Abiraterone<br>* CYP17 inhibitor<br>* Other names: Zytiga;|
| Experimental: ADT, Abiraterone and Apalutamide<br>Goserelin 10.8 mg, single dose, subcutaneously. Abiraterone 1,000 mg, once daily, orally for 3 months. Prednisone 5 mg, once daily, orally for 3 months. Apalutamide 240 mg, once daily, orally for 3 months. | Drug: Goserelin<br>* Androgen Deprivation Therapy<br>* Other names: ADT;Drug: Prednisone<br>* Corticosteroid<br>Drug: Abiraterone<br>* CYP17 inhibitor<br>* Other names: Zytiga;Drug: Apalutamide<br>* Androgen-receptor antagonist<br>* Other names: ARN-509;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic response | To compare the rate of pathologic complete response (pCR) or pathologic near complete response (pnCR), defined as less than 0,5 cm of residual tumor in the prostatectomy specimen after neoadjuvant therapy. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Residual cellularity rate | To compare the rate of residual cellularity ≤ 30% in the prostatectomy specimen after neoadjuvant therapy. | 3 months | 
| Pathologic downgrading | To compare the rate of pathologic downgrading to ≤ ypT2N0 in the prostatectomy specimen after neoadjuvant therapy. | 3 months | 
| PSA decline rate | To compare the rate of PSA decline ≥ 50% and 90% after 3 months of neoadjuvant therapy. | 3 months | 
| Rate of positive surgical margins | To compare the rate of positive surgical margins in the prostatectomy specimen after neoadjuvant therapy. | 3 months | 
| Rate of undetectable PSA | To compare the rate of patients with undetectable PSA 12 months after radical prostatectomy. | 12 months | 
| Rate of Grade ≥ 3 CTCAE adverse events | To compare the rate of CTCAE grade 3 or higher adverse events of the neoadjuvant therapy arms | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant therapy, High-risk Prostate Cancer