Neoadjuvant Therapy of Abiraterone Plus ADT for High Risk Prostate Cancer

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Abiraterone Acetate; Drug: Prednisone; Drug: Goserelin 10.8 mg

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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 robotic assisted radical prostatectomy	Drug: Abiraterone Acetate; 1000 mg orally daily for 24 weeks before robotic assisted radical prostatectomy; Drug: Prednisone; 5 mg oral low dose prednisone, once daily; Drug: Goserelin 10.8 mg; 10.8 mg goserelin hypodermic once per 12 weeks
EXPERIMENTAL: ADT alone; 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; 10.8 mg goserelin hypodermic once per 12 weeks

What is the study measuring?

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
Recovery time of urinary continence (day)	The recovery time of urinary continence (day) after radical prostatectomy, defined as 0 pad/day.	12 month
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
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

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2019
• Primary Completion (ACTUAL): March 1, 2021
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: April 12, 2020
• First Submitted That Met QC Criteria: April 19, 2020
• First Posted (ACTUAL): April 22, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 16, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Goserelin; Prednisone; Abiraterone Acetate
• Other Study ID Numbers: IUNU-PC-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No