In Situ Clonal Heterogeneity in Prostatic Diagnostic Biopsies

NCT04873427 | Terminated

• 1 other identifier: CLM_RAD_001
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a retrospective, proof of concept study, which aims at reconstructing the cellular heterogeneity of the tumor in multi-needle diagnostic prostate biopsy as well as any biopsy containing potentially pre-malignant tissue, to study its implications in the clinical history of the disease. For each patient, 2 or more samples will be prepared starting from the FFPE diagnostic material. The biopsy used for assigning the Gleason score will be sequenced, together with two or more of the local peri-proximal biopsies with a higher level of differentiation. Samples will undergo Whole Exome Sequencing with an average coverage of 300x at the Wellcome Sanger Institute (WSI, Hinxton, UK). Sequencing data will be analysed for single nucleotide variants, copy number variants and structural variants by using state-of-the-art data analysis pipeline at WSI.

1. 1.Reconstruction of local PCa heterogeneity in multi-needle diagnostic biopsy with different Gleason scores (6-10) using high-coverage whole exome sequencing (WES) and DP-based clonal analysis;
2. 2.Characterization of the relationships between pathological differentiation (Gleason score) and genomics-measured heterogeneity and malignancy features;
3. 3.Assessment of clinical implications of clonal heterogeneity.

Conditions

Prostate Cancer; Genetic Predisposition

Keywords

Prostate Cancer; genetic heterogeneity; personalized medicine

Outcome Measures

Primary Outcomes (1)

• reconstruction of local PCa heterogeneity

  Primary endpoint is the reconstruction of local PCa heterogeneity in multi-needle diagnostic biopsy with different Gleason scores (6-10) using high-coverage whole exome sequencing (WES) and DP-based clonal analysis

  through study completion, an average of 2 years

Secondary Outcomes (1)

• relationships between pathological differentiation (Gleason score) and genomics-measured heterogeneity

  through study completion, an average of 2 years

Study Arms (2)

early metastatic prostate cancer patients

Reconstruction of local PCa heterogeneity in multi-needle diagnostic biopsy with different Gleason scores (6-10) using high-coverage whole exome sequencing (WES) and DP-based clonal analysis

Genetic: clonal heterogeneity evaluation

non-relapsing/non-metastatic patients with indolent malignant disease

Reconstruction of local PCa heterogeneity in multi-needle diagnostic biopsy with different Gleason scores (6-10) using high-coverage whole exome sequencing (WES) and DP-based clonal analysis

Genetic: clonal heterogeneity evaluation

Interventions

clonal heterogeneity evaluation GENETIC

Reconstruction of local PCa heterogeneity in multi-needle diagnostic biopsy with different Gleason scores (6-10) using high-coverage whole exome sequencing (WES) and DP-based clonal analysis

early metastatic prostate cancer patients; non-relapsing/non-metastatic patients with indolent malignant disease

Eligibility Criteria

• Gender Eligibility Details: male as we are investigated prostate cancer
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

patients with prostate cancer

You may qualify if:

• a local disease with Gleason ≤ 7 (3+4, i.e. more differentiated tissue is found in diagnostic biopsies, better overall prognosis)
• no metastasis whatsoever during the follow-up;
• an advanced prostatic neoplasia with Gleason score ≥ 7 (4+3, i.e. less differentiated tissue is found in diagnostic biopsies, worse overall prognosis)
• multiple synchronous or metachronous metastasis.

You may not qualify if:

• insufficient material on the tissue biopsy to be left in archives for further evaluations/analyses;
• insufficient amount of tumor cells at baseline;

Sponsors & Collaborators

• Clinica Luganese Moncucco: lead

Study Sites (1)

Alessandra Franzetti Pellanda

Lugano, Canton Ticino, 6900, Switzerland

Location

Related Publications (23)

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Biospecimen

Retention: SAMPLES WITH DNA

prostatic diagnostic biopsies

MeSH Terms

Conditions

Prostatic Neoplasms; Genetic Predisposition to Disease

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alessandra Franzetti Pellanda, MD

  Clinica Luganese Moncucco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 28, 2021
• First Posted: May 5, 2021
• Study Start: April 15, 2021
• Primary Completion: January 15, 2023
• Study Completion: January 15, 2023
• Last Updated: February 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)