Clinical trial NCT04736108: Neoadjuvant Therapy of Abiraterone Plus ADT for Intraductal Carcinoma of the Prostate
Official title: A Single-center, Phase II Neoadjuvant Study of Abiraterone Acetate in the Treatment of Intraductal Carcinoma of the Prostate
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: abiraterone acetate
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2021-02-03
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Pathologic Complete Response Rate（pCR）
timeFrame: 6 months
Secondary outcomes:
measure: Rate of Subjects With Minimal Residual Disease
timeFrame: 6 months
measure: Rate of positive surgical margin (PSM)
timeFrame: 6 months
measure: Rate of Nodal Metastases After 6 Months of Treatment
timeFrame: 6 months
measure: Rate of Pathologic T3 Disease After 6 Months of Treatment
timeFrame: 6 months
measure: Biochemical Progression-free Survival (bPFS)
timeFrame: 2 years
measure: PSA decline rate
timeFrame: 6 months
measure: Incidence and severity of adverse events
timeFrame: 6 months
measure: Quality of life (QOL) as assessed by FACT-P
timeFrame: Up to 24 months after surgery
measure: Quality of life as assessed by EQ-5D
timeFrame: Up to 24 months after surgery
measure: Radiographic progression-free survival (rPFS)
timeFrame: 2 years
measure: Overall survival
timeFrame: 5 years
Other outcomes:
measure: Rate of Magnetic Resonance Imaging Downstaging after Neoadjuvant Therapy
timeFrame: 6 months
measure: Exploratory analysis to correlate tissue expression of PSA, CYP17, Ki67, and AR with pathologic response
timeFrame: 6 months
Locations:
city: Chengdu
country: China
facility: West China Hospital
state: Sichuan
Study officials:
affiliation: West China Hospital
name: Hao Zeng, Professor
role: PRINCIPAL_INVESTIGATOR
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