UZ/KU Leuven Program for Post-mortem Tissue Donation to Enhance Research (UPTIDER)

UPTIDER is a prospective, interventional, non-Investigational Medicinal Product (non-IMP), non-commercial, single centre post-mortem tissue donation program for metastatic breast cancer patients or patients with a germline pathogenic variant with a moderate to high lifetime risk of breast cancer and at least one malignancy at time of death. The overarching objective of UPTIDER is (i) to unravel metastatic breast cancer evolution, biology, heterogeneity and treatment resistance and (ii) to assess pathogenicity and tumour biology in hereditary cancer syndromes with a high lifetime risk of breast cancer; both through extensive post-mortem multi-level and multi-region sample analysis.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Hereditary Diseases
• Intervention / Treatment: Procedure: Blood draw; Procedure: Post-mortem tissue collection

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Giuseppe Floris, MD PhD; Phone Number: 003216336539; Email: giuseppe.floris@uzleuven.be
• Study Contact Backup: Name: Christine Desmedt, PhD; Phone Number: www.ltbcr.be 003216193306; Email: christine.desmedt@kuleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
    • Contact: Josephine Van Cauwenberge, MD; Phone Number: 0032493364654; Email: josephine.vancauwenberge@kuleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Signature of informed consent by the subject.
• Metastatic breast cancer, or hereditary cancer syndrome with a moderate to high lifetime risk of breast cancer, for which the patient is treated/followed in UZ Leuven or treated in another hospital and referred to UZ Leuven specifically for the trial.

Additional inclusion criteria for the different substudies:

• Pilot phase: no additional inclusion criteria.
• ILC substudy: histologically confirmed history of ILC.
• IBC substudy: history of IBC, fulfilling the following criteria described by Dawood et al: rapid onset of breast erythema, oedema and/or peau d'orange and/or warm breast with or without an underlying palpable mass, duration of history of no more than 6 months, erythema occupying at least one-third of the breast and pathological confirmation of invasive carcinoma.
• Hereditary cancer syndrome substudy: confirmed presence of a germline mutation known to be associated with a moderate to high lifetime risk of BC (e.g. known pathogenic variants in the genes BRCA1/2, CHEK2, TP53, PALB2) and presence of at least one malignant lesion at time of inclusion (of any origin) .
• Other substudies: no additional inclusion criteria.

Exclusion Criteria:

• Presence of a transmissible disease that can form a risk to the health of researchers or others handling the body or patient samples. This includes but is not limited to the following infectious diseases: human immunodeficiency virus (HIV), active hepatitis C virus (HCV), encephalitis of unknown cause, Creutzfeldt-Jakob disease, rabies, active malaria, active tuberculosis, active SARS-CoV-2 infection.
• Presence of any factors that could logistically or organizationally impede the study or the performance of sampling within a reasonable post-mortem time frame. This includes but is not limited to: residence of the subject at a faraway distance from the UZ Leuven hospital; residence of the subject on territory outside of Belgium; impossibility to notify the clinician confirming the death and the researchers within a reasonable time frame in case of death.

Additional exclusion criteria for the different substudies:

- ILC substudy, IBC substudy: diagnosis of a malignancy other than breast cancer in the 5 years prior to inclusion. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin and in situ cervical carcinoma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Standard; UPTIDER consists of 8 substudies: Pilot phase; Invasive Lobular Carcinoma (ILC) substudy; Inflammatory Breast Cancer (IBC) substudy; Molecular heterogeneity and treatment response substudy; Patient-derived xenograft (PDX) / Patient-derived Organoid (PDO) substudy; Metabolomics substudy; Liquid biopsy substudy; Hereditary cancer syndromes substudy The intervention, consisting of sample collection only, is identical in all substudies, however, the focus of downstream analysis of the samples may be different.

Procedure: Blood draw; Blood draw at inclusion; Procedure: Post-mortem tissue collection; Sample collection (both liquids, tumour tissue and non-tumour tissue) during post-mortem research autopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients consenting to participate in the pilot phase	Should be equal to or above 50%	Baseline
Median time elapsed between moment of death and start of the autopsy	Should be equal to or less than 12h	During autopsy
Median time elapsed between collection of first and last sample	Should be equal to or less than 8h	During autopsy
Percentage of metastatic organs sampled	Should be equal to or more than 75%	During autopsy
Percentage of samples with sufficient quality of DNA extracted	A260/A280 ratio	During autopsy
Percentage of samples with sufficient quality of RNA extracted	RNA integrity number (RIN)	During autopsy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concordance between TILs and clinical response to treatment	Standard histopathological review	During autopsy
Rate of T cell exhaustion	RNA sequencing	During autopsy
Number of mutations in each tumor lesion	Whole exome sequencing	During autopsy
Type of mutations in each tumor lesion	Whole exome sequencing	During autopsy
Percentage of Tumour Infiltrating Lymphocytes (TILs)	Standard histopathological review	During autopsy

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: KU Leuven; Universiteit Antwerpen

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Estimated): September 1, 2035
• Study Completion (Estimated): September 1, 2035

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 24, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): June 28, 2024
• Last Update Submitted That Met QC Criteria: June 27, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn
• Other Study ID Numbers: S64410

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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