Neoadjuvant Therapy of Abiraterone Plus ADT for High Risk Prostate Cancer

Study Overview
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Brief Summary
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High risk prostate cancer (PCa) had worse outcomes on radical treatment results, short-time oncological results, even cancer-specific survival, than those low or mediate risk PCa. Neoadjuvant treatment before radical prostatectomy had been proven to get some benefits on peri-operation results, especially on reduction of tumor volume and minimization of biochemical recurrence. This study will evaluate the efficacy and safety of androgen deprivation therapy (ADT) with abiraterone in neoadjuvant therapy for surgically resectable high-risk or very high-risk PCa.

Official Title
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Medical Ethics Committee of Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Abiraterone Acetate
* Drug: Prednisone
* Drug: Goserelin 10.8 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be ≥ 18 and ≤75 years of age. All patients must have a histologically or cytologically diagnosis of prostate cancer and must be eligible for radical prostatectomy. All patients must undergo thorough tumor staging and meet one of the following criteria: 1. multi-parameter MRI or PSMA PET / CT shows clinical staging of primary tumor ≥ T3, 2. Gleason score of primary tumor ≥ 8, 3. prostate specific antigen (PSA) ≥20 ng/ml. Eastern Cooperative Oncology Group (ECOG) physical condition score ≤ 1 Patients must have adequate hematologic function, within 28 days prior to registration as evidenced by: white blood cell (WBC) ≥ 4.0 × 109 / L, platelets≥ 100 × 109 / L, hemoglobin ≥ 9 g / dL, and international normalized ratio (INR) < 1.5. Patients must have adequate hepatic function, within 28 days prior to registration, as evidenced by: total bilirubin (TBIL)≤1.5 x upper limit of normal (ULN),and SGOT (AST) and SGPT (ALT) ≤ 2.5 x ULN. Patients must have adequate renal function, within 28 days prior to registration, as evidenced by serum creatinine ≤2×ULN Patients must participate voluntarily and sign an informed consent form (ICF), indicating that they understand the purpose and required procedures of the study, and are willing to participate in. Patients must be willing to obey the prohibitions and restrictions specified in the research protocol. Exclusion Criteria: Patients with prostate having neuroendocrine, small cell, or sarcoma-like features are not eligible. Patients with low-risk and medium-risk, localized prostate cancer (the following conditions are met at the same time) are not eligible: multi-parameter MRI or PSMA PET / CT shows clinical staging of primary tumor < T3, Gleason score of primary tumor < 8, and prostate specific antigen (PSA) <20 ng/ml. Patients with clinical or radiological evidence of regional or extra-regional lymph node metastases or bone metastases or visceral metastases are not eligible. Patients with clinical or radiological evidence of regional or extra-regional lymph node metastases or bone metastases or visceral metastases are not eligible. Patients who have previously received androgen deprivation therapy (medical or surgical) or focal treatment of prostate cancer or prostate cancer radiotherapy or prostate cancer chemotherapy are not eligible. Patients with severe or uncontrolled concurrent infections are not eligible. Patients must not have New York Heart Association Class III or IV congestive heart failure at the time of screening. Patients must not have any thromboembolic event, unstable angina pectoris, myocardial infarction within 6 months prior to registration. Patients must not have uncontrolled severe hypertension, persistent uncontrolled diabetes, oxygen-dependent lung disease, chronic liver disease, or HIV infection. Patients must not have had other malignancies other than prostate cancer in the past 5 years, but cured basal cell or squamous cell skin cancers can be enrolled. Patients with mental illness, mental disability or inability to give informed consent are not eligible.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADT with Abiraterone and prednisone<br>All subjects in this arm will receive luteinizing hormone releasing hormone analogue (LHRHa) plus abiraterone acetate and prednisone, as per standard of care. Goserelin 10.8 mg will be used once per 12 weeks. Abiraterone acetate will be administered orally as 1000 mg once daily along with 5 mg of oral prednisone once per day. Subjects will continue to take abiraterone acetate and prednisone for 24 weeks before robotic assisted radical prostatectomy | Drug: Abiraterone Acetate<br>* 1000 mg orally daily for 24 weeks before robotic assisted radical prostatectomy<br>Drug: Prednisone<br>* 5 mg oral low dose prednisone, once daily<br>Drug: Goserelin 10.8 mg<br>* 10.8 mg goserelin hypodermic once per 12 weeks<br>|
| Experimental: ADT alone<br>All subjects in this arm will receive LHRHa alone for 24 weeks before receiving robotic assisted radical prostatectomy. Goserelin 10.8 mg will be administered once per 12 weeks. | Drug: Goserelin 10.8 mg<br>* 10.8 mg goserelin hypodermic once per 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response Rate | The proportion of subjects with no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy | up to 8 months | 
| Proportion of Subjects With Minimal Residual Disease | The proportion of subjects that have residual tumors with maximum diameter of 5 mm or less after radical prostatectomy | up to 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Stage Degradation | Clinical or pathological stage degradation after neoadjuvant therapy | up to 8 months | 
| Rate of Positive Surgical Margins | The proportion of subjects with positive surgical margins after radical prostatectomy | up to 8 months | 
| Rate of Complete Serum Remission | The proportion of subjects whose PSA is less than or equal to 0.2 ng/ml after 6 months of treatment | up to 6 months | 
| Proportion of subjects without PSA progression | The proportion of subjects whose PSA has never gone below 1 ng/ml or who receive any radiotherapy or systemic treatment after radical prostatectomy | 24 months | 
| Imaging Response Rate | The proportion of subjects whose primary tumor is in complete remission on imaging or residual tumor's maximum diameter is less than 0.5cm | up to 8 months | 
| Recovery time of urinary continence (day) | The recovery time of urinary continence (day) after radical prostatectomy, defined as 0 pad/day. | 12 month | 
| biochemical recurrence-free survival (bRFS) | biochemical recurrence-free survival (bRFS) defined as time to PSA ≥ 0.2 ng/ml after radical prostatectomy. | 3 years | 
| metastasis-free survival (MFS) | time from date of randomization to date of evidence of systemic disease on bone scan or cross-sectional imaging. | 5 years |