Clinical trial NCT04983628: Molecular Profiling in Prostate Cancer
Official title: Prognostic and Predictive Value of Tumor Molecular Alterations in Patients With Prostate Cancer
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Prostate Cancer Metastatic
Prostate Cancer Recurrent
Germline BRCA1 Gene Mutation
Germline BRCA2 Gene Mutation
Mutation
Keywords: Prostate cancer
Predictive biomarker
Prognostic biomarker
Lead sponsor: Hellenic Cooperative Oncology Group
Sponsor class: OTHER
First posted: 2021-07-30
Enrollment: 250
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with metastatic, recurrent, locally advanced or "intermediate or high risk" (Gleason \>7), operable prostate cancer

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Prevalence of germline and somatic mutations in cancer predisposing genes
timeFrame: 1 year
Secondary outcomes:
measure: Overall survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Hellenic Cooperative Oncology Group
Study officials:
affiliation: HeCOG
name: Elena Fountzila
role: PRINCIPAL_INVESTIGATOR
References: