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

Neoadjuvant Therapy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05376722
• Other study ID #: IUNU-PC-111
• Status: Recruiting
• Phase: Phase 2
• Start date: February 22, 2022
• Est. completion date: September 2024

Study information

• Verified date: October 2022
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: hongqian guo, Dr.
• Phone: 13605171690
• Email: dr.ghq[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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;

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 2024
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neoadjuvant Therapy
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
China	Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University	Nanjing	Jiangsu
China	Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University	Nanjing	Jiangsu
China	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School	Nanjing	Jiangsu

Sponsors (4)

Lead Sponsor	Collaborator
Hongqian Guo	First Affiliated Hospital of Zhejiang University, Nanjing First Hospital, Nanjing Medical University, The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Rate of Positive Surgical Margins	The proportion of subjects with positive surgical margins after radical prostatectomy	up to 8 months
Secondary	Downstaging rate of radical prostatectomy	Downstaging rate of radical prostatectomy	four months to 2 years after surgery
Secondary	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
Secondary	PSA response rate	The proportion of subjects with a =98% reduction in nadir PSA from baseline PSA during neoadjuvant therapy	up to 2 years