Clinical trial NCT05376722: A Study of Pamiparib Combined With Abiraterone Acetate in Neoadjuvant Treatment of Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Neoadjuvant Therapy
Keywords: pamiparib
abiraterone acetate
high-risk prostate cancer
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Zhejiang University
name: The First Affiliated Hospital of Soochow University
name: Nanjing First Hospital, Nanjing Medical University
First posted: 2022-05-17
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

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;

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: up to 6months
Secondary outcomes:
measure: AEs/SAEs
timeFrame: Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first
measure: 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
timeFrame: 3 years
measure: Rate of Positive Surgical Margins
timeFrame: up to 8 months
measure: Downstaging rate of radical prostatectomy
timeFrame: four months to 2 years after surgery
measure: Pathological response rate of neoadjuvant patients with HRR gene mutation
timeFrame: four months to 2 years after surgery
measure: PSA response rate
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University
state: Jiangsu
city: Nanjing
country: China
facility: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University
state: Jiangsu
city: Nanjing
country: China
facility: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
state: Jiangsu
Study officials:
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: shun zhang, Dr.
role: PRINCIPAL_INVESTIGATOR
References: