Prevalence of HRR-related Genes Mutations and Prognosis in Metastatic Castration Resistant Prostate Cancer (mCRPC) Patients in Real World Setting (ZENSHIN)

The purpose of this study is to investigate the prevalence of tissue homologous recombination repair (HRR)-related gene mutations (positive/negative/Variant of uncertain significance (VUS)), clinical outcome such as prostate-specific antigen-progression free survival (PSA-PFS), overall survivals (OS) and treatment pattern in mCRPC patients.

<Methods> Study design: multi-center, prospective cohort study

Data Source(s):

In this study, 155 patients (expected recruitment patients: maximum 205 patients) will be enrolled from approximately 20~30 sites in Japan. Study Population: mCRPC patients who diagnosed between 2014 and 2018. Exposure(s): N.A Outcome(s): Prevalence of tissue HRR-related gene mutations, clinical outcomes such as Over survival and PSA-PFS, Treatment pattern

Sample Size Estimations:

The target population is 155 patients based on the prevalence of HRR-related genes (BRCA1, BRCA2 and ATM) which is reported in previous global study (PROfound study).

Statistical Analysis:

This study is not intended to verify specific hypotheses, and the results are evaluated descriptively. There is no plan of interim analyses before the final analysis.

Study Overview

• Status: Completed
• Conditions: Prostatic Neoplasms

• Study Type: Observational
• Enrollment (Actual): 205

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan
    • Chiba University Hospital
  • Gifu, Japan
    • Gifu University Hospital
  • Kyoto, Japan
    • Kyoto Prefectural University of Medicine
  • Miyazaki, Japan
    • University of Miyazaki Hospital
  • Okayama, Japan
    • Okayama University Hospital
  • Aichi
    • Nagoya, Aichi, Japan
      • Nagoya University Hospital
    • Nagoya, Aichi, Japan
      • Nagoya City University Hospital
  • Aomori
    • Hirosaki, Aomori, Japan
      • Hirosaki University Hospital
  • Chiba
    • Kashiwa, Chiba, Japan
      • Jikei University Kashiwa Hospital
  • Ehime
    • Toon, Ehime, Japan
      • Ehime University Hospital
  • Hiroshima
    • Kure, Hiroshima, Japan
      • National Hospital Organization Kure Medical Center
  • Hokkaido
    • Hakodate, Hokkaido, Japan
      • Hakodate Goryoukaku Hospital
    • Sapporo, Hokkaido, Japan
      • Hokkaido University Hospital
    • Sapporo, Hokkaido, Japan
      • Sapporo Medical University Hospital
  • Hyogo
    • Kobe, Hyogo, Japan
      • Kobe City Medical Center General Hospital
    • Kobe, Hyogo, Japan
      • Kobe University Hospital
  • Ibaraki
    • Tsukuba, Ibaraki, Japan
      • University of Tsukuba Hospital
  • Ishikawa
    • Kanazawa, Ishikawa, Japan
      • Kanazawa University Hospital
  • Kagawa
    • Miki, Kagawa, Japan
      • Kagawa University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan
      • Yokohama City University Medical Center
    • Yokohama, Kanagawa, Japan
      • Yokohama City University Hospital
  • Nara
    • Kashihara, Nara, Japan
      • Nara Medical University Hospital
  • Osaka
    • Osakasayama, Osaka, Japan
      • Kindai University Hospital
  • Saitama
    • Kawagoe, Saitama, Japan
      • Saitama Medical Center
  • Tottori
    • Yonago, Tottori, Japan
      • Tottori University Hospital
  • Yamaguchi
    • Ube, Yamaguchi, Japan
      • Yamaguchi University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Probability Sample

Study Population

The target population is mCRPC patients who diagnosed between 2014 and 2018 and be confirmed to be succeeded HRR-related gene mutation analysis with archived primary or metastatic tumor sample. As median of expected overall survival of mCRPC is 2.5 to 3 years from diagnosis, follow up period is enough to measure outcomes including survival. The baseline period is set to calculate overall survival and to detect clinical outcome at least half. The patients will be enrolled consecutively to this study.

Description

Inclusion Criteria:

• Age > 20, Japanese men at the time of informed consent.
• Patients who provided informed consent. If the patient has died, opt-out will be applicable.
• Patients who are diagnosed as mCRPC between January 1st in 2014 and December 31st in 2018.
• Patients who have a FFPE tumor sample (primary or metastatic) with Formalin Neutral Buffer Solution.
• Patients which the investigator judges to secure the enough amount of tumor samples for future laboratory test.

Exclusion Criteria:

• Patients who have failed HRR-related gene mutation testing with the myChoice HRD plus in screening period.
• Patients who have an only FFPE primary tumor sample (primary or metastatic) with unbuffered formalin including acidic formalin.
• Patients who have taken an investigational medical product for prostate cancer from Jan 1st , 2014 to Dec 31st 2020.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of tissue HRR-related gene mutations	Calculate number and prevalence of each HRR-related gene mutation status (Positive/Negative/VUS), respectively. Prevalence will be accompanied by 95% Clopper-Pearson confidence intervals.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of each treatment pattern	The number (%) of patients by treatment pattern in 1st line treatment, 2nd line, and 3rd line treatment after diagnosed as mCRPC, respectively, will be calculated.	From index date(diagnosed as mCRPC) patients to December 31 2020

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient's characteristics including stratified by tissue HRR-related gene mutations in mCRPC patients	Patient's characteristics will be summarized.	Baseline
PSA50 response	PSA50 response will be analysed based on baseline and nadir PSA value in each treatment.	From index date(diagnosed as mCRPC) to december 31 2020

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• Redacted CSR Synopsis

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 29, 2020
• Primary Completion (ACTUAL): December 18, 2020
• Study Completion (ACTUAL): December 18, 2020

Study Registration Dates

• First Submitted: May 21, 2020
• First Submitted That Met QC Criteria: June 8, 2020
• First Posted (ACTUAL): June 11, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 7, 2021
• Last Update Submitted That Met QC Criteria: November 30, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: metastatic castration resistant prostate cancer, BRCA1, BRCA2, ATM, Homologous recombination repair
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: D081LR00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials/studies via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved, AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No