The Added Value of Tissue or Liquid Biopsy NGS Profiling in Advanced Solid Tumor Treatment Decisions.

Official title

The Added Value of Tissue or Liquid Biopsy NGS Profiling in Advanced Solid Tumor Treatment Decisions: The Belgian PRECISION Study of the BSMO in Collaboration With the Cancer Center of Sciensano.

Overview

A total of 550 patients with metastatic solid tumors or primary CNS malignancy will be recruited on a first come first serve basis at one of the 14 participating centers : UZL, UZG, Imelda, ZAZ, AZ Klina, CHU Liège, GHdC, CHU UCL Namur, IJB, UZB, CUSL, UZA, VITAZ and Jessa Zh.. \> 500 patients with tissue available will undergo CGP centrally at UZ Leuven (Roche AVENIO Tumor Tissue CGP kits, Novaseq platform). \> 50 patients without tissue available will undergo liquid biopsy testing at Foundation Medicine (FoundationOne Liquid CDx). The sequencing data generated by UZ Leuven laboratory will then be further analysed (secondary and tertiary analysis) by one of the eight laboratories participating in the study: UZL, UZG, IJB, CUSL, IPG, UZA, Jessa zh. and CHU Liège.

Detailed description

GeNeo 2.0 Study PRIMARY OBJECTIVE AND ENDPOINTS

To describe the genomic landscape of advanced solid tumors and primary CNS cancer as evaluated by CGP of tumor or ctDNA (for all included patients and tumor types separate). To do so, following calculations will be performed :

* Prevalence of ESCAT level 1, 2, 3 or 4 alterations based on MTB discussion of Roche AVENIO Tumor Tissue CGP kit results. * Prevalence of ESCAT level 1, 2, 3 or 4 alterations based on MTB discussion of Foundation One Liquid CDx results. * Prevalence of genomic alterations according to altered gene, type of variant of tumor type.

GeNeo 2.0 Study SECONDARY OBJECTIVES AND ENDPOINTS

1. To describe the number of patients receiving a treatment recommendation by the MTB. 2. To describe the uptake of the MTB recommendations. 3. To evaluate the treatment recommendations proposed by the MTB. 4. To evaluate the reasons for discordance between the actual treatment and MTB recommendation. 5. To evaluate the turnaround time of tumor CGP and ctDNA testing. 6. To evaluate the technical success rate of tumor CGP and ctDNA testing. 7. To evaluate the impact of CGP on patient referral and trial inclusion.

All secondary analyses will be performed for all included patients, for tumor/ctDNA CGP testing and for tumor types separate. To do so, following calculations will be performed :

* Proportion of patients receiving at least 1 MTB recommendation * Proportion of patients with at least 1 MTB recommendation that initiated the recommended treatment. * Qualitative and quantitative descriptive analysis of treatment recommendations proposed by the MTB. * Descriptive analysis of reasons for discordance between actual treatment and MTB recommendations. * Proportion of patients with a time between sample pick-up and MTB report ≤28 days. * Proportion of patients in which tumor CGP and ctDNA testing failed for technical reasons + descriptive analysis of potential reasons. * Descriptive analysis of patient referrals between centers for participation in genotype-driven clinical trials.

Interventions

• Diagnostic test Comprehensive NGS testing
  To determine the Added Value of Tissue and Liquid Biopsy NGS profiling in Advanced Solid Tumor Treatment Decisions: The Belgian PRECISION study of the BSMO in collaboration with the Cancer Center of Sciensano (GeNeo 2.0)

Primary outcome measures

• Distribution of ESCAT Actionability Levels Identified by Comprehensive Genomic Profiling [Time frame: Through study completion, an average of 1 year.]
• Distribution of Genomic Alteration Types Identified by Comprehensive Genomic Profiling [Time frame: Through study completion, an average of 1 year.]

Secondary outcome measures (5)

• Number of patients receiving a treatment recommendation [Time frame: Through study completion, an average of 1 year.]
• % of uptake of the MTB recommendations [Time frame: Through study completion, an average of 1 year.]
• Treatment recommendations quality. [Time frame: Through study completion, an average of 1 year.]
• Participants whose treatment differed from the Molecular Tumor Board recommendation [Time frame: Through study completion, an average of 1 year.]
• Participants with turnaround time within 28 days [Time frame: Through study completion, an average of 1 year.]

Eligibility criteria

Inclusion criteria

• Adult patient (minimum 18 years) able to provide written informed consent for GeNeo 2.0.
• ECOG Performance status ≤2
• Patients with advanced solid tumors or primary CNS tumors that are candidates for systemic anticancer therapy and open for enrollment in a potential downstream therapeutic trial. Enrollment in early treatment lines is strongly encouraged Tumor cohorts of breast cancer and lung cancer will be prioritized, with a minimum cap of 100 for each tumor type. Recruitment for all other tumor type cohorts will be capped at a maximum of 40 patients per tumor type. The MTB can decide on prematurely closing or extending tumor type cohorts based on treatment recommendations, clinical trial landscape or downstream treatment options. Enrollment of patients early in the advanced treatment setting will be strongly encouraged.
• Patients should have archived tissue available from a metastatic (preferred) or primary lesion biopsy for comprehensive profiling. The tissue should not be more than 2 years-old and fixed in 10% neutral buffered formalin. Tumor cell content should be >20%

Exclusion criteria

• Life expectancy of ≤12 weeks according to the local investigator
• Clinically significant hematopoietic, renal and/or hepatic dysfunction, according to the local investigator, which would make them ineligible for MGTO therapy
• Patients unwilling to comply with GeNeo 2.0 protocol data collection, data sharing and other study procedures
• Patients unwilling to provide informed consent and comply with study procedures.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Belgium · 14 centers

• Institute Jules Bordet — Anderlecht
• ZAS — Antwerp
• Imelda — Bonheiden
• AZ Klina — Brasschaat
• Universitaire Ziekenhuis Antwerpen — Edegem
• UZ Gent — Ghent
• GHDC — Gilly
• Jessa Ziekenhuis — Hasselt
• … and 6 more centers

Identifiers

NCT: NCT07713550 · BSMO 2024-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗