Clinical trial NCT04531696: UZ/KU Leuven Program for Post-mortem Tissue Donation to Enhance Research
Official title: UZ/KU Leuven Program for Post-mortem Tissue Donation to Enhance Research
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Hereditary Diseases
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: KU Leuven
name: Universiteit Antwerpen
First posted: 2020-08-28
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of patients consenting to participate in the pilot phase
timeFrame: Baseline
measure: Median time elapsed between moment of death and start of the autopsy
timeFrame: During autopsy
measure: Median time elapsed between collection of first and last sample
timeFrame: During autopsy
measure: Percentage of metastatic organs sampled
timeFrame: During autopsy
measure: Percentage of samples with sufficient quality of DNA extracted
timeFrame: During autopsy
measure: Percentage of samples with sufficient quality of RNA extracted
timeFrame: During autopsy
Secondary outcomes:
measure: Concordance between TILs and clinical response to treatment
timeFrame: During autopsy
measure: Rate of T cell exhaustion
timeFrame: During autopsy
measure: Number of mutations in each tumor lesion
timeFrame: During autopsy
measure: Type of mutations in each tumor lesion
timeFrame: During autopsy
measure: Percentage of Tumour Infiltrating Lymphocytes (TILs)
timeFrame: During autopsy
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
References: