Circulating Tumor DNA (ctDNA) Monitoring in the Assessment and Prediction of the Efficacy of PARP Inhibitors (PARPi)

Study Overview
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Brief Summary
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To evaluate the application value of customized ctDNA monitoring in efficacy assessment and prediction during PARPi treatment

Detailed Description
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This clinical study is an open-label, single-center, observational study to evaluate the application value of customized ctDNA monitoring in efficacy assessment and prediction during PARPi treatment in mCRPC patients. A total of 30 participants with second-line treatment failure will be registered in this study. Whole blood collection will be conducted during the treatment for ctDNA detection, homologous recombination repair (HRR) genes testing, personalized panel customization and whole exome sequencing.

Official Title
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Circulating Tumor DNA (ctDNA) Monitoring in the Assessment and Prediction of the Efficacy of PARP Inhibitors (PARPi)

Conditions
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Metastatic Castration-resistant Prostate Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet ALL of the following criteria: Willing and able to provide informed consent. Adult males from 18 to 75 years age. History of histologically or cytologically confirmed adenocarcinoma of the prostate with DDR genes mutation (BRCA1/2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L) detected by high throughput sequencing Documented evidence of metastatic castration resistant prostate cancer (mCRPC) and proposed treatment of PARP inhibitors. Evidence of measurable target lesion in imaging studies. Participants can provide adequate formalin fixed paraffin-embedded (FFPE) tumor tissue collected before any treatment: tumor cell content>30% and necrotic cells<10%. ECOG performance status 0-1 Estimated survival≥12 weeks Exclusion Criteria: Patients must NOT meet any of the following criteria: Do not meet the inclusion criteria. Under any other anti-tumor therapy like chemotherapy and/or immunotherapy. Receiving organ transplantation in the last 3 months. Participants with autoimmune diseases or history of HBV, HCV or HIV infection (acute or chronic). Participants with pneumonia. Severe concurrent illness or co-morbid disease that would make the subject unsuitable for enrolment Unwilling and unable to provide informed consent. Patients who are judged unsuitable for clinical trial participation by the investigators. Elimination Criteria: Violation of the prescribed rule of medication that may influence the judgment of curative effect and safety.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiological progression free survival (rPFS) | Radiological progression free survival (rPFS) - defined as the time from randomisation to radiological progression, assessed by investigator per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 (soft tissue) and Prostate Cancer Working Group-3 (PCWG-3) criteria (bone), or death from any cause, or the last follow-up, whichever occurs first | From date of randomisation to until radiographic progression (up to 1 year) | 
| Objective Response Rate (ORR) | ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). Per RECIST v1.1, CR=Disappearance of all target lesions; PR = >=30% decrease in the sum of diameters of target lesions; For each treatment group, ORR is the number of patients with a CR and PR. | From randomisation until radiographic progression (up to 1 year) | 
| PSA response rate | PSA response rate is defined as the proportion of patients with a PSA decline (defined as a ≥30%, ≥50% and other declines in PSA from baseline). | From randomisation until radiographic progression (up to 1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as time from treatment commencement to death of any cause | 2 years |