LEVANTIS-0087A: GAGomes for Multi-Cancer Early Detection in Asymptomatic Adults (LEV87A)

Study Overview
=================
Brief Summary
-----------------
LEVANTIS-0087A (LEV87A) is a retrospective in vitro diagnostics clinical validation population cohort-based case-control study to validate the diagnostic performance of free GAGome-based tests for multi-cancer early detection (MCED) in adults asymptomatic for cancer and with no recent history of cancer.

Detailed Description
-----------------
Multi-cancer early detection (MCED) could prevent 26% of all cancer-related deaths - an effect larger than averting all deaths from breast cancer alone. However, a societal program to implement MCED requires a practical, noninvasive, and affordable diagnostic modality that is sensitive and specific to all forms of cancers. Liquid biopsies represent front-runner modalities to this end but virtually all of them rely on genomics biomarkers, typically circulating free DNA (cfDNA), which capture <20% of cancers in stage I. In addition, they miss certain cancer types that shed little cfDNA, like brain or genitourinary tumors. Pilot studies show that free glycosaminoglycan profiles in plasma and urine, or free GAGomes, were promising noninvasive biomarkers of cancer metabolism that detected over a third of stage I cancers across 14 types, including brain and genitourinary tumors. LEVANTIS-0087A (LEV87A) is a retrospective in vitro diagnostics clinical validation population cohort-based case-control study to develop free GAGome-based tests for multi-cancer early detection in adults asymptomatic for cancer and with no recent history of cancer (Sub-Study 1) and to validate their diagnostic performance in the target population (Sub-Study 2). LEV87A uses retrospectively collected biospecimens from one or more population-based biobanks representative of the target population.

Official Title
-----------------
LEVANTIS-0087A: GAGomes for Multi-Cancer Early Detection in Asymptomatic Adults (LEV87A)

Conditions
-----------------
Cancer

Intervention / Treatment
-----------------
* Diagnostic Test: Combined free GAGome MCED test


Participation Criteria
=================
Eligibility Criteria
-----------------
Sub-Study 1 Inclusion Criteria Case Arm: At the baseline visit, >18 years old, any gender At the baseline visit, available biospecimens for both EDTA-plasma and urine Diagnosis of cancer before or at the baseline visit or diagnosis of cancer after the baseline visit If a diagnosis of cancer before or at the baseline visit, then no antineoplastic treatment between the date of diagnosis and the baseline visit Control Arm: At the baseline visit, >18 years old, any gender Not receiving treatment for or under surveillance for cancer at the baseline visit No indications of being monitored for or under consideration for suspected cancer at the baseline visit No diagnosis of cancer before or on the baseline visit or if any previous diagnosis of cancer, then cancer must have been curatively treated ≥ 5 years before the baseline visit No diagnosis of cancer within at least 365 days after the baseline visit At the baseline visit, available biospecimens for both EDTA-plasma and urine Exploratory Arm: Same as Control Arm and type 2 diabetes or hypertension or BMI > 30 at the baseline visit Exclusion Criteria Case Arm: No available data for diagnosis of cancer starting 90 days before the baseline visit and up to 365 days after the baseline visit A subject with only a self-reported diagnosis of cancer (either in the 90 days before or in the 365 days after the baseline visit), and absence of a histopathological or clinically indicated diagnosis of cancer, according to biobank database(s), or through linkage with cancer registry(ies) Control Arm and Exploratory Arm: No available data for diagnosis of cancer up to 365 days after or on the baseline visit A histopathological or clinically indicated diagnosis of cancer within 365 days from the baseline visit, according to biobank database(s), or through linkage with cancer registry(ies) Sub-Study 2 Inclusion Criteria At the baseline visit, 35 - 80 years old, any gender Not receiving treatment for or under surveillance for cancer at the baseline visit No indications of being monitored for or under consideration for suspected cancer at the baseline visit No diagnosis of cancer before or on the baseline visit or if any previous diagnosis of cancer, then cancer must have been curatively treated ≥ 5 years before the baseline visit At the baseline visit, available biospecimens for both EDTA-plasma and urine Exclusion Criteria No available data for diagnosis of cancer up to 365 days after the baseline visit A subject with only a self-reported diagnosis of cancer in the 365 days after the baseline visit and absence of a histopathological or clinically indicated diagnosis of cancer, according to biobank database(s), or through linkage with cancer registry(ies) Subjects not meeting the specifications for the target population eventually changed during test development in Sub-Study 1. Note that these specifications are pre-specified in the Statistical Analysis Plan and will be applied if they meet pre-specified acceptance criteria.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sub-Study 1<br>Adults >= 18 years old with cancer or imminent cancer diagnosis (cases) versus cancer-free and no imminent cancer diagnosis (controls). Sub-Study 1 is intended for the development of 3 free GAGome MCED tests. | Diagnostic Test: Combined free GAGome MCED test<br>* The combined free GAGome MCED test aggregates measurements of plasma and urine GAGomes (the exhaustive human glycosaminoglycan profile) into a diagnostic score, the combined free GAGome MCED score. The measurements are performed using MIRAM MCED Kits (Elypta AB) and the scores are computed using Elypta SKY Software (Elypta AB)<br>|
| Sub-Study 2<br>Adults between 35 - 80 years old asymptomatic for cancer and with no recent history of cancer (> 5 years since curative-intent treatment for cancer). Sub-Study 2 is intended for the validation of the combined free GAGome MCED test (primary endpoint) and the plasma and urine free GAGome MCED tests (secondary endpoints). | Diagnostic Test: Combined free GAGome MCED test<br>* The combined free GAGome MCED test aggregates measurements of plasma and urine GAGomes (the exhaustive human glycosaminoglycan profile) into a diagnostic score, the combined free GAGome MCED score. The measurements are performed using MIRAM MCED Kits (Elypta AB) and the scores are computed using Elypta SKY Software (Elypta AB)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of the combined free GAGome MCED test | Indicative of any-type cancer vs. no cancer diagnosis | Within 365 days after the baseline visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of the plasma free GAGome MCED test | Indicative of any-type cancer vs. no cancer diagnosis | Within 365 days after the baseline visit | 
| Sensitivity and specificity of the urine free GAGome MCED test | Indicative of any-type cancer vs. no cancer diagnosis | Within 365 days after the baseline visit | 
| Accuracy to the putative cancer location (PCL) model in the case (cancer) arm | Accuracy to the putative cancer location (PCL) model in the case (cancer) arm | Within 365 days after the baseline visit | 
| Overall survival (OS) in the case (cancer) arm | Overall survival (OS) in the case (cancer) arm | From baseline visit until the date of death from any cause, assessed up to 15 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
liquid biopsy, multi-cancer early detection, glycosaminoglycans