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

Sponsor

West China Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04736108

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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）.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Abiraterone acetate Drug: Prednisolone Drug: Goserelin	Phase 2

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

May 1, 2021

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ADT with Abiraterone and prednisone 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 1000 mg orally daily for 24 weeks before radical prostatectomy Drug: Prednisolone 5 mg oral low dose prednisone, once daily Drug: Goserelin 10.8 mg goserelin hypodermic once per 12 weeks

Arm

Intervention/Treatment

Experimental: ADT with Abiraterone and prednisone

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

1000 mg orally daily for 24 weeks before radical prostatectomy

Drug: Prednisolone

5 mg oral low dose prednisone, once daily

Drug: Goserelin

10.8 mg goserelin hypodermic once per 12 weeks

Outcome Measures

Primary Outcome Measures

Pathologic Complete Response Rate（pCR） [6 months]
The proportion of subjects with no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy.

Secondary Outcome Measures

Rate of Subjects With Minimal Residual Disease [6 months]
The proportion of subjects that have residual tumors with maximum diameter of 5 mm or less after radical prostatectomy.
Rate of positive surgical margin (PSM) [6 months]
The rate of positive surgical margins in the prostatectomy specimen after neoadjuvant therapy.
Rate of Nodal Metastases After 6 Months of Treatment [6 months]
The rate of the presence of tumor cells within surgically excised lymph nodes will be assessed after 6 months of neoadjuvant treatment.
Rate of Pathologic T3 Disease After 6 Months of Treatment [6 months]
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.
Biochemical Progression-free Survival (bPFS) [2 years]
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.
PSA decline rate [6 months]
The rate of PSA decline to baseline PSA after 6 months of neoadjuvant therapy.
Incidence and severity of adverse events [6 months]
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.
Quality of life (QOL) as assessed by FACT-P [Up to 24 months after surgery]
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.
Quality of life as assessed by EQ-5D [Up to 24 months after surgery]
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.
Radiographic progression-free survival (rPFS) [2 years]
Time from surgery to radiographic progression or death
Overall survival [5 years]
Time from surgery to death due to any cause

Other Outcome Measures

Rate of Magnetic Resonance Imaging Downstaging after Neoadjuvant Therapy [6 months]
The rate of MRI imaging downstaging after neoadjuvant therapy
Exploratory analysis to correlate tissue expression of PSA, CYP17, Ki67, and AR with pathologic response [6 months]
To correlate the expression of PSA, CYP17, Ki67, and AR by immunohistochemistry with pCR/npCR in the prostatectomy specimen.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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