A Study of Pamiparib Combined With Abiraterone Acetate in Neoadjuvant Treatment of Prostate Cancer

A Prospective Clinical Study of the Safety and Efficacy of Pamiparib Combined With Abiraterone Acetate in Neoadjuvant Treatment of High-risk or Very High-risk Localized Prostate Cancer

To evaluate the pathological response rate of pamiparib combined with abiraterone acetate in neoadjuvant therapy for surgically resectable high-risk or very high-risk prostate cancer after radical prostatectomy

Study Overview

• Status: Recruiting
• Conditions: Neoadjuvant Therapy
• Intervention / Treatment: Drug: pamiparib; Drug: abiraterone; Drug: prednisone

Detailed Description

the main purpose: To evaluate the pathological response rate of pamiparib combined with abiraterone acetate in neoadjuvant treatment of surgically resectable high-risk or very high-risk prostate cancer after radical prostatectomy; Note: pathological response rate = pathological complete response rate (pCR) + minimal residual disease (MRD)(defined as residual tumor with the largest crosssection dimension ≤5 mm OR RCB≤0.25CM³)

Secondary purpose:

1. To evaluate the safety of pamiparib combined with abiraterone acetate as neoadjuvant therapy for high-risk or very high-risk prostate cancer;
2. To evaluate the rate of PSA biochemical recurrence-free survival (bPFS) at 1 year after radical prostatectomy in neoadjuvant treatment of high-risk or very-high-risk prostate cancer with pamiparib combined with abiraterone acetate;
3. The positive rate of surgical margins in radical prostatectomy;
4. Downstaging rate of radical prostatectomy;
5. Pathological response rate of neoadjuvant patients with HRR gene mutation;

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: hongqian guo, Dr.; Phone Number: 13605171690; Email: dr.ghq@163.com
• Study Contact Backup: Name: shun zhang, Dr.; Phone Number: 15050589789; Email: explorershun@126.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University
      • Contact: Junlong Zhuang, MD; Phone Number: 8615950451917; Email: zhuangjl-2008@163.com
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Inclusion Criteria:

  1. Men aged ≥18 years and ≤80 years old.
  2. Patients with prostate cancer diagnosed by histology or cytology who are suitable for radical prostatectomy.

  3. All patients meet at least one of the following criteria:

     1. Multiparametric MRI and PSMA PET/CT scan or CT scan showing primary tumor stage ≥ T3;
     2. Primary tumor Gleason score ≥ 8;
     3. Serum PSA concentration ≥ 20 ng/ml;
     4. Imaging assessment has regional lymph node metastasis (N1);
  4. Eastern Cooperative Oncology Group (ECOG) performance status score≤1

  5. Laboratory inspections meet the following requirements:

     Blood routine: white blood cell count (WBC) ≥3.0×109/L, platelet count ≥100×109/L, hemoglobin ≥9g/dl; renal function: serum creatinine ≤2×ULN; liver function: alanine aminotransferase (ALT) and Aspartate aminotransferase (AST)≤2.5×ULN, total bilirubin TBIL≤1.5×ULN; coagulation function: international normalized ratio (INR)<1.5.

  6. The subjects participate voluntarily, and the subjects themselves must sign the Informed Consent Form (ICF), indicating that they understand the purpose and required procedures of this research, and are willing to participate in the research. Subjects must be willing and comply with the prohibitions and restrictions set forth in the study protocol.
  7. During the treatment, the testosterone level in the blood is reduced to the "castration" level, and the testosterone level is less than 50ng/dL;
  8. The subjects can understand and are willing to sign the informed consent

Exclusion Criteria:

• Exclusion Criteria:

  1. Patients with neuroendocrine, small cell, or sarcomatoid features on prostate histopathology.
  2. Low- and intermediate-risk localized prostate cancer (all the following conditions are met) (PSA<20 ng/mL; Gleason score<8; clinical stage<T3).
  3. Patients with clinical or radiological evidence suggestive of extraregional lymph node metastasis or bone or visceral metastasis (any M1).
  4. Received androgen deprivation therapy (including drug or surgical castration) for more than 3 months or focal prostate cancer treatment or prostate cancer radiotherapy and chemotherapy in the past.
  5. Patients with severe or uncontrolled concurrent infections.
  6. Suffering from New York Heart Association (NYHA) class III/IV congestive heart failure, unstable angina or a history of myocardial infarction within the past 6 months.
  7. Uncontrolled severe hypertension, persistent uncontrolled diabetes, oxygen-dependent lung disease, chronic liver disease, or HIV infection.
  8. In the past 5 years, other malignancies other than prostate cancer, but cured basal or squamous cell skin cancer can be enrolled.
  9. Suffering from mental illness, mental disability or inability to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: pamiparib; Subjects received pamiparib 40 mg orally, twice a day; abiraterone acetate 1000 mg orally, once a day; prednisone acetate tablets (prednisone) 5 mg, once a day; every 30 days Treatment cycle, treatment for 4-6 cycles, that is, 4-6 months. Robot-assisted laparoscopic radical prostatectomy and extended lymph node dissection within 30 days of the end of 4 months of neoadjuvant therapy. If the subjects have intolerable toxic reactions during the treatment period, the dose adjustment can be carried out. Day 1 of cycle 1, day 15 and day 1±3 days of each cycle thereafter, and 1 follow-up within 30 days after the end of treatment and before surgery; 1 prostate MRI during the screening period and within 30 days after the end of treatment and before surgery Scan, PSMA PET/CT scan or CT scan

Drug: pamiparib; pamiparib 40 mg orally, twice a day; Drug: abiraterone; biraterone acetate 1000 mg orally, once a day; Drug: prednisone; prednisone acetate tablets (prednisone) 5 mg, once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the pathological response rate of pamiparib combined with abiraterone acetate in neoadjuvant therapy for surgically resectable high-risk or very high-risk prostate cancer after radical prostatectomy	To evaluate the pathological response rate of pamiparib combined with abiraterone acetate in neoadjuvant therapy for surgically resectable high-risk or very high-risk prostate cancer after radical prostatectomy	up to 6months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs/SAEs	The level of AEs defined by NCI-CTCAE v5.0. Safety assessments will be assessed and documented after initiation of study drug, regardless of relationship to study drug. The level of complications defined by Clavien-Dindo classification.	Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first
Rate of Positive Surgical Margins	The proportion of subjects with positive surgical margins after radical prostatectomy	up to 8 months
PSA response rate	The proportion of subjects with a ≥98% reduction in nadir PSA from baseline PSA during neoadjuvant therapy	up to 2 years
the 1-year PSA biochemical recurrence-free survival (bPFS) rate after radical prostatectomy in neoadjuvant therapy of paamiparib combined with abiraterone acetate in high- or very-high-risk prostate cancer	Defined as the proportion of patients who did not experience biochemical progression or death within 3 years of initiation of pamiparib treatment; biochemical progression was defined as an increase in serum PSA level to >0.2 ng/ml with 2 consecutive increases at least 3 months apart	3 years
Downstaging rate of radical prostatectomy	Downstaging rate of radical prostatectomy	four months to 2 years after surgery
Pathological response rate of neoadjuvant patients with HRR gene mutation	Pathological response rate of neoadjuvant patients with HRR gene mutation	four months to 2 years after surgery

Collaborators and Investigators

• Sponsor: Hongqian Guo
• Collaborators: First Affiliated Hospital of Zhejiang University; Nanjing First Hospital, Nanjing Medical University; The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2022
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: May 13, 2022
• First Posted (Actual): May 17, 2022

Study Record Updates

• Last Update Posted (Actual): January 5, 2023
• Last Update Submitted That Met QC Criteria: January 3, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: abiraterone acetate; high-risk prostate cancer; pamiparib
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: IUNU-PC-111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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