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

Breast Cancer Clinical Trial

— UPTIDER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04531696
• Other study ID #: S64410
• Status: Recruiting
• Phase: N/A
• Start date: November 30, 2020
• Est. completion date: September 2035

Study information

• Verified date: December 2022
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: Giuseppe Floris, MD PhD
• Phone: 003216336539
• Email: giuseppe.floris[@]uzleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 2035
• Est. primary completion date: September 2035
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Genetic Diseases, Inborn
• Hereditary Diseases

Intervention

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

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven

Sponsors (3)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven	KU Leuven, Universiteit Antwerpen

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients consenting to participate in the pilot phase	Should be equal to or above 50%	Baseline
Primary	Median time elapsed between moment of death and start of the autopsy	Should be equal to or less than 12h	During autopsy
Primary	Median time elapsed between collection of first and last sample	Should be equal to or less than 8h	During autopsy
Primary	Percentage of metastatic organs sampled	Should be equal to or more than 75%	During autopsy
Primary	Percentage of samples with sufficient quality of DNA extracted	A260/A280 ratio	During autopsy
Primary	Percentage of samples with sufficient quality of RNA extracted	RNA integrity number (RIN)	During autopsy
Secondary	Concordance between TILs and clinical response to treatment	Standard histopathological review	During autopsy
Secondary	Rate of T cell exhaustion	RNA sequencing	During autopsy
Secondary	Number of mutations in each tumor lesion	Whole exome sequencing	During autopsy
Secondary	Type of mutations in each tumor lesion	Whole exome sequencing	During autopsy
Secondary	Percentage of Tumour Infiltrating Lymphocytes (TILs)	Standard histopathological review	During autopsy