Radiotherapy Combined With Fluzopanib and Abiraterone Acetate Tablets (II) Treatment for mCRPC

Official title

An Open, Single Arm, Multicenter Clinical Study on the First-line Treatment of Metastatic Castration Resistant Prostate Cancer With Radiotherapy Combined With Fuzuloparib and Abiraterone Acetate Tablets（Ⅱ）

Overview

This study is an open label, single arm, multicenter clinical trial. The aim of this study is to evaluate the efficacy, safety, and quality of life of radiotherapy combined with Fuzuloparib and Abiraterone Acetate Tablets（Ⅱ） as first-line treatment for castration resistant prostate cancer patients. The study aims to enroll 40 eligible subjects with PSA response rate (PSA 50) as the primary endpoint.

Detailed description

This study is an open-label, single-arm, multicenter clinical trial designed to evaluate the efficacy, safety, and quality of life of first-line treatment with the combination of radiotherapy, fluzoparib, abiraterone acetate (II) for patients with metastatic castration-resistant prostate cancer (mCRPC).Eligible subjects who meet the inclusion criteria will be enrolled and assessed for Homologous Recombination Repair (HRR) mutation status. Participants will undergo two phases of treatment: the induction phase and the maintenance phase. During the induction phase, patients will receive Intensity-Modulated Radiation Therapy (IMRT) in combination with fluzoparib, abiraterone acetate (II), and prednisone. In the maintenance phase, patients will continue treatment with fluzoparib, abiraterone acetate (II), and prednisone. Each treatment cycle is 28 days long, and treatment will continue until disease progression is determined by the investigator and the patient is no longer clinically benefiting from the study. Follow-up will continue until the subject withdraws informed consent or the study ends, whichever occurs first.The study plans to enroll 40 eligible subjects. The primary endpoint is the PSA response rate (the proportion of patients with a ≥50% decrease in PSA from baseline). Secondary endpoints include radiographic progression-free survival (rPFS), time to PSA progression (TTPP), PSA depth of response (PSA 90, PSA undetectable rate), time to first subsequent treatment (TFST), failure-free survival (FFS), and overall survival (OS).

Interventions

• Drug Intensity-modulated radiation therapy (IMRT) in combination with fluzoparib, abiraterone acetate tablets (II), and prednisone.
  Induction therapy, fluzoparib (150mg BID orally), abiraterone acetate tablets (II) (300mg QD orally), and prednisone (5mg BID orally). IMRT was administered as follows: For patients with low metastatic burden tumors: Prostate ± pelvic lymph node radiation + metastatic lesion radiation.For patients with non-low metastatic burden tumors: Prostate±pelvic lymph node radiation.IMRT dosage:Prostate: 70 Gy in 28 fractions (2.5 Gy/fraction, 5 fractions per week).Pelvic lymph nodes: 50.4 Gy in 28 fractio

Primary outcome measures

• PSA relief rate [Time frame: The duration from the first day of patient enrollment to the time when PSA decreases by ≥ 50% compared to baseline should not exceed 12 months.]

Secondary outcome measures (6)

• Radiographic Progression-free survival（rPFS） [Time frame: The duration of evaluation from the first day of patient enrollment to the time of radiological progression should not exceed 60 months.]
• Time To PSA Progression（TTPP） [Time frame: The duration of evaluation from the first day of patient enrollment to the time of PSA progression should not exceed 60 months.]
• PSA deep relief rate [Time frame: The duration from the first day of patient enrollment to the time when PSA decreases by ≥ 90% from baseline and the lowest PSA value is ≤ 0.2ng/ml should not exceed 12 months.]
• Time To First Subsequent Therapy（TFST） [Time frame: The duration from the first day of patient enrollment to the start of any subsequent prostate cancer treatment should not exceed 60 months.]
• Failure-free Survival（FFS） [Time frame: The duration of evaluation from the first day of patient enrollment to any degree of disease progression should not exceed 60 months.]
• Overall survival（OS） [Time frame: The duration from the first day of patient enrollment to all-cause mortality rate should not exceed 60 months.]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years old, male
• ECOG score is 0 or 1
• Untreated first-line metastatic castration resistant prostate cancer patients
• Allow the use of a new endocrine drug treatment once during hormone sensitive stages
• The organ function level must meet the following requirements (no blood transfusion or hematopoietic growth factor therapy received within 2 weeks before blood routine screening): ANC ≥ 1.5 × 109/L PLT≥100×109/L； • Hb≥90 g/L； • TBIL ≤ 1.5 × ULN (excluding subjects with Gilbert syndrome) • ALT and AST ≤ 2.5 × ULN; • Cr≤1.5×ULN； • LVEF≥50%； • QTcF≤450 ms。
• If the partner is a subject with fertility, they should undergo surgical sterilization or agree to receive it during and at the end of the trial period
• Sign a written informed consent form and expect good compliance with the research protocol

Exclusion criteria

• Previously received any PARPi treatment for prostate cancer (including but not limited to Olaparib, Nilaparib, Terazopanib, Lucaparib, etc.)
• Other clinical trial drug treatments and major surgeries received within the 4 weeks prior to randomization in this study
• There are factors such as inability to swallow, chronic diarrhea and intestinal obstruction, or other factors that affect medication intake and absorption
• Have a history of epilepsy or have experienced a disease that can trigger epileptic seizures within the 12 months prior to randomization (including a history of transient ischemic attacks, stroke, traumatic brain injury with consciousness disorders requiring hospitalization)
• Active heart disease within the first 6 months of randomization, including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure (heart function class III or IV), and drug-induced ventricular arrhythmias
• Individuals with active HBV and HCV infection (HBsAg positive and virus copy number ≥ 500 IU/mL, HCV antibody positive and HCV RNA above the detection limit of the analytical method)
• Individuals with a known history of allergies to Fluzopanib and Abiraterone nanocrystals and their components
• Individuals with a history of congenital immunodeficiency or organ transplantation, or HIV positive subjects who meet one or more of the following criteria: Not receiving highly effective antiretroviral therapy; Change antiretroviral therapy within 6 months prior to the start of screening; • Undertaking antiretroviral therapy that may interfere with the investigational drug (please consult the sponsor before enrollment); CD4 count<350/mm3 during screening; Opportunistic infections that meet the definition of acquired immunodeficiency syndrome occurred within the 12 months prior to the start of screening
• Patients with other malignant tumors within the past 3 years prior to randomization (excluding in situ cancer that has completely resolved and malignant tumors judged by researchers to have slow progression)
• The researchers determined that participants with ejaculation ability and sexual activity were unwilling to take the contraceptive measures specified in the protocol during the entire study treatment period and within 3 months after the last dose

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of China Medical University — Shenyang

Identifiers

NCT: NCT06971211 · FirstHCMU-JBi-PARTOM

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗