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

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

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Jun Wang, M.D.; Phone Number: +020-87343656; Email: wangjun2@sysucc.org.cn
• Study Contact Backup: Name: Yonghong Li, M.D.; Phone Number: +020-87343656; Email: liyongh@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Yonghong Li, M.D.; Phone Number: +020-87343656; Email: liyongh@sysucc.org.cn
      • Contact: Fangjian Zhou, M.D.; Phone Number: +020-87343656; Email: zhoufj@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

clinic-based sample

Description

Inclusion Criteria:

Patients must meet ALL of the following criteria:

1. Willing and able to provide informed consent.
2. Adult males from 18 to 75 years age.
3. History of histologically or cytologically confirmed adenocarcinoma of the prostate with Homologous Recombination Deficiency or DDR genes mutation (BRCA1/2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L) detected by high throughput sequencing
4. Documented evidence of metastatic castration resistant prostate cancer (mCRPC) and proposed treatment of PARP inhibitors.
5. Evidence of measurable target lesion in imaging studies.
6. Participants can provide adequate formalin fixed paraffin-embedded (FFPE) tumor tissue collected before any treatment: tumor cell content>30% and necrotic cells<10%.
7. ECOG performance status 0-1
8. Estimated survival≥12 weeks

Exclusion Criteria:

Patients must NOT meet any of the following criteria:

1. Do not meet the inclusion criteria.
2. Under any other anti-tumor therapy like chemotherapy and/or immunotherapy.
3. Receiving organ transplantation in the last 3 months.
4. Participants with autoimmune diseases or history of HBV, HCV or HIV infection (acute or chronic).
5. Participants with pneumonia.
6. Severe concurrent illness or co-morbid disease that would make the subject unsuitable for enrolment
7. Unwilling and unable to provide informed consent.
8. 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Yonghong Li, M.D., Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2021
• Primary Completion (Actual): March 31, 2023
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: November 1, 2021
• First Submitted That Met QC Criteria: November 1, 2021
• First Posted (Actual): November 11, 2021

Study Record Updates

• Last Update Posted (Estimated): September 5, 2024
• Last Update Submitted That Met QC Criteria: August 31, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 2021-FXY-171

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No