Molecular Profiling in Prostate Cancer (ProProstate)

Prognostic and Predictive Value of Tumor Molecular Alterations in Patients With Prostate Cancer

We aim to employ targeted DNA NGS to evaluate the prevalence of germline and somatic mutations in cancer predisposing genes, such as BRCA1 and BRCA2, and other HR and DDR genes, including also a few additional clinically relevant genes, in patients with metastatic, locally advanced or high-grade prostate cancer. In addition, we will investigate the prognostic role of these mutations as well as their association with various clinicopathological parameters. This will be the first study investigating the prevalence of germline and somatic pathogenic mutations in Greek patients with prostate cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer Recurrent; Prostate Cancer Metastatic; Mutation; Germline BRCA1 Gene Mutation; Germline BRCA2 Gene Mutation
• Intervention / Treatment: Other: Tumor molecular profiling

Detailed Description

This study will include formalin-fixed paraffin-embedded tumor tissue (FFPE) from 250 patients with metastatic, recurrent, locally advanced or "intermediate or high risk" (Gleason >7), operable prostate cancer. FFPE tumor blocks alongside peripheral blood will be retrieved for all patients from Pathology Laboratories. Available FFPE blocks will be subjected to histological review by an experienced pathologist to evaluate H&E sections for confirmation of diagnosis, histologic type, grade and tumor cell content (TCC%), as well as mark tumor dense areas for manual macro-dissection, prior to DNA extraction, in order to enrich samples for tumor DNA. Clinicopathologic characteristics of patients with prostate cancer will be retrieved from their respective medical records. Diagnosis will be confirmed through pathology reports, which will also provide information about Gleason Score and histological subtype.

In all instances, the collection of patient information will be in compliance with the regulations of the Bioethics committees of participating Hospitals. The study will be conducted in accordance with the principles of the Helsinki Declaration of Human Rights.

Following manual macro-dissection, FFPE tumor tissue material will be processed for DNA extraction, according to standard procedures with the QIAamp DNA Mini Kit (Qiagen GmbH, Hilden, Germany).

Sequencing will be performed at the Laboratory of Molecular Oncology, using an Ion Torrent Proton Sequencer (Life Technologies/Ion Torrent). For the purpose of targeted NGS genotyping of tumor and available matched germline DNA samples, we designed a custom Ampliseq panel to target coding relevant regions of genes involved in homologous recombination (HR), along with several others.

Data retrieval and base calling will be performed on the Torrent Server (v5.8.0.8). Consequently, we will then employ appropriate Ion Reporter Workflows (version 5.10) to automatically annotate single nucleotide variants (SNVs), multiple nucleotide variants (MNVs), small insertions / deletions (INDELs) and copy number variations (CNVs).

• Study Type: Observational
• Enrollment (Actual): 250

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 11524
    • Hellenic Cooperative Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Patients with metastatic, recurrent, locally advanced or "intermediate or high risk" (Gleason >7), operable prostate cancer

Description

Inclusion Criteria:

• metastatic prostate cancer
• recurrent prostate cancer
• locally advanced prostate cancer
• "intermediate or high risk" (Gleason >7), operable prostate cancer
• available FFPE tumor tissue

Exclusion Criteria:

• absence of tumor tissue available for analysis

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of germline and somatic mutations in cancer predisposing genes	Number of patients with either germline or somatic mutations	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from diagnosis to the date of death, through the completion of the study	3 years

Collaborators and Investigators

• Sponsor: Hellenic Cooperative Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): January 30, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: February 16, 2021
• First Submitted That Met QC Criteria: July 20, 2021
• First Posted (Actual): July 30, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Prostate cancer; Prognostic biomarker; Predictive biomarker
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: TR_9/21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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