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

Hongqian Guo

Status and phase: Enrolling; Phase 2

Conditions: Neoadjuvant Therapy

Treatments: Drug: pamiparib; Drug: prednisone; Drug: abiraterone

Study type: Interventional

Funder types: Other

Identifiers

NCT05376722

IUNU-PC-111

Details and patient eligibility

About

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

Full 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;

Enrollment: 30 estimated patients

Sex: Male

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

30 participants in 1 patient group

pamiparib

Experimental group

Description:

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

Treatment:

Drug: pamiparib

Drug: prednisone

Drug: abiraterone