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

Study Overview
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Brief Summary
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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.

Official Title
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UZ/KU Leuven Program for Post-mortem Tissue Donation to Enhance Research

Conditions
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Breast Cancer, Hereditary Diseases

Intervention / Treatment
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* Procedure: Blood draw
* Procedure: Post-mortem tissue collection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard<br>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<br>* Blood draw at inclusion<br>Procedure: Post-mortem tissue collection<br>* Sample collection (both liquids, tumour tissue and non-tumour tissue) during post-mortem research autopsy<br>|

What is the study measuring?
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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 |