Neoadjuvant Therapy of Abiraterone Plus ADT for Intraductal Carcinoma of the Prostate

Study Overview
=================
Brief Summary
-----------------
Neoadjuvant treatment before radical prostatectomy has been proven to provide 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 abiraterone acetate Plus androgen deprivation therapy（ADT）in high-risk localized prostate cancer with intraductal carcinoma of the prostate（IDC-P）.

Detailed Description
-----------------
IDC-P is an adverse pathological entity of prostate cancer, characterized by the growth of malignant cells in pre-existing prostatic ducts and acini, and is present in high-grade disease and associated with poor prognosis. Previous studies have shown that IDC-P was significantly associated with an adverse clinical course in patients who received radical prostatectomy or radiotherapy, and the presence of IDC-P on the biopsy specimen was associated with a poor prognosis in terms of overall survival (OS) and a poor docetaxel response in patients with distant metastasis at the initial diagnosis. Our previous researches as well as other published data indicated that abiraterone had a better therapeutic efficacy than docetaxel as the first-line therapy in metastatic castration resistance prostate cancer（mCRPC）with IDC-P. Therefore we intended to perform this single-arm phase II clinical trial to evaluate the initial efficacy and safety of abiraterone acetate Plus ADT as neoadjuvant therapy for high-risk localized prostate cancer with IDC-P. The primary endpoint is the pathologic complete response (pCR).

Official Title
-----------------
A Single-center, Phase II Neoadjuvant Study of Abiraterone Acetate in the Treatment of Intraductal Carcinoma of the Prostate

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Abiraterone acetate
* Drug: Prednisolone
* Drug: Goserelin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years Histologically or cytologically diagnosis of prostate cancer with positive IDC-P status High-risk localized prostate cancer, defined by either: Tumor stage ≥T3a by digital rectal examination, or Primary tumor Gleason score ≥ 8, or PSA > 20 ng/mL No evidence of metastases The ECOG score of the patient is ≤2 Expected survival over 5 years 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 Agree to collect the tumor tissue and blood samples needed for the research and apply them to related study Adequate hematologic, renal and hepatic function: Absolute neutrophil count [ANC] ≥1.5 x 10^9/L Platelet count [PLT] ≥100 x 10^9/L Hemoglobin [HGB] ≥9 g/dL Serum Total bilirubin [TBIL] ≤1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 2.5 x ULN Serum albumin [ALB] ≥2.8 g/dL Serum Creatinine ≤ 1.5 x ULN Creatinine Clearance ≥ 40 mL/min Exclusion Criteria: Prior androgen deprivation therapy (medical or surgical), radiation therapy or chemotherapy for prostate cancer Evidence of metastatic disease (M1) on imaging studies Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate Major surgery or severe trauma within 30 days before enrollment Patients with severe or uncontrolled concurrent，including but not limited to： Severe or uncontrolled concurrent infections Human immunodeficiency virus [HIV] infection positive Suffer from acute or chronic active hepatitis B (HBsAg positive and HBV DNA>1x10^3/mL) Or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA>15 IU/mL) Active tuberculosis, etc Abnormal cardiac function as manifested by NYHA (New York Heart Association) class III or IV heart failure，or clinically significant ventricular arrhythmias Uncontrolled hypertension（Systolic blood pressure≥160mmHg or Diastolic blood pressure≥100mmHg） Severe or unstable angina, myocardial infarction，arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks) Occurred within 6 months before enrollment 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 Any condition that in the opinion of the investigator, would preclude participation in this study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group 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 radical prostatectomy | Drug: Abiraterone acetate<br>* 1000 mg orally daily for 24 weeks before radical prostatectomy<br>Drug: Prednisolone<br>* 5 mg oral low dose prednisone, once daily<br>Drug: Goserelin<br>* 10.8 mg goserelin hypodermic once per 12 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response Rate（pCR） | The proportion of subjects with no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate 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. | 6 months | 
| Rate of positive surgical margin (PSM) | The rate of positive surgical margins in the prostatectomy specimen after neoadjuvant therapy. | 6 months | 
| Rate of Nodal Metastases After 6 Months of Treatment | The rate of the presence of tumor cells within surgically excised lymph nodes will be assessed after 6 months of neoadjuvant treatment. | 6 months | 
| Rate of Pathologic T3 Disease After 6 Months of Treatment | The rate of the presence of T3 disease (e.g. extraprostatic tumor not invading adjacent structures) will be determine from the prostatectomy specimen after 6 months of neoadjuvant treatment. | 6 months | 
| Biochemical Progression-free Survival (bPFS) | Biochemical progression will be defined per the American Urological Association guidelines (i.e. confirmed prostate-specific antigen post-radical prostatectomy >= 0.2 ng/mL) or death. Will be estimated using Kaplan-Meier methods and 95% CI will be estimated using Greenwood's formula. | 2 years | 
| PSA decline rate | The rate of PSA decline to baseline PSA after 6 months of neoadjuvant therapy. | 6 months | 
| Incidence and severity of adverse events | Safety as assessed by the incidence and severity of adverse events and serious adverse events graded according to the National Cancer Institute - Common Terminology Criteria for adverse events (CTCAE) version 4.0. | 6 months | 
| Quality of life (QOL) as assessed by FACT-P | The QOL will be measured using the functional assessment of cancer therapy-prostate（FACT-P）. The questionnaires will be administered at baseline, prior to RP and every 3 months for 2 years post RP. | Up to 24 months after surgery | 
| Quality of life as assessed by EQ-5D | The QOL will be measured using the EuroQol five dimensions questionnaire（EQ-5D）. The questionnaires will be administered at baseline, prior to RP and every 3 months for 2 years post RP. | Up to 24 months after surgery | 
| Radiographic progression-free survival (rPFS) | Time from surgery to radiographic progression or death | 2 years | 
| Overall survival | Time from surgery to death due to any cause | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
abiraterone acetate