A Study to Examine the Value of Broad Agnostic Next Generation Sequencing (NGS) Panel Testing Versus Reimbursed Organ-directed NGS: a Belgian Precision Study of the BSMO in Collaboration With the Cancer Center
NCT ID: NCT04641676
Last Updated: 2021-05-28
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
NA
1000 participants
INTERVENTIONAL
2020-10-09
2022-12-31
Brief Summary
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This context is unfavorable with regard to the following issues:
1. Many more additional drugs with sound scientific rationale and preclinical evidence are available through clinical trials. The relevant genes are generally not included in the reimbursed NGS and ad hoc identification of such patients is extremely difficult and thus severely hampering the accrual in such trials. This denies patients a potential access to innovative treatments from which they could benefit and hampers progress.
2. The same genes can be mutated in other cancer types, other than the reimbursed context, but are not detected due to the organ-specific approach in reimbursed NGS. Examination of these genes with an agnostic approach would give these other patients potential access to the drugs (via various routes, including clinical trials or medical need or otherwise)
3. The broader panels applied by some Belgian platforms (50-100 genes), sometimes in an agnostic approach, do not cover all potentially actionable genes or not all types of actionable variants in these genes.
4. Rearrangements which are highly actionable are not systematically covered in NGS testing, but rely on immunohistochemistry (if done at all) of fusion panels testing that requires additional funding.
5. The various Belgian NGS labs use accredited but heterogeneous methodology and it has been reported that the detection rate of some mutations varies from one site to another.
Therefore, from a patient and oncologist point of view there are current deficiencies that jeopardize optimal access of patients to current or novel genome-driven therapies. Defective identification of sensitive patients limits the implementation of clinical trials and their accrual rates and therefore the attractiveness of Belgium for such trials.
There are more comprehensive commercial platforms that cover a large set of actionable genes (up to hundreds of genes) and the various types of mutations in these genes: sequence mutations, rearrangements, resulting in fusion genes, and gene amplifications.
These commercial vendors have adequate comprehensive methodology but are too expensive (at their current public pricing) for general application. One of these is the platform of Foundation Medicine that builds on a large experience in variant annotation in the US and includes probably all current actionable targets including gene mutations, fusions, MSI, and TMB, all at once in one result. They also report actionability and established or clinical trial treatment options.
To oncologists this is very attractive compared to the fragmented, sequential and very limited current reimbursed conditions.
The investigators estimate that up to 20% of advanced cancer patients could get access to genotype-based treatment that are not covered by the organ-based reimbursement based access to NGS. This can be in the form of off-label application of reimbursed drugs, pharma-sponsored drug development trials that address a specific genotype or pharma sponsored or academic basket trials. Without broad agnostic testing the identification of eligible patients remains extremely difficult. A recent study \[A study of genetic characteristics and suitability for targeted cancer treatment (TARGET)\] showed that the rate of detection of actionable mutations increased from 28% with local testing to 66% with Foundation Medicine testing.
Objectives
1. To determine the added value of comprehensive and agnostic NGS versus "real-world" practice ("real-world" practice means local testing, no reimbursement for local testing and/or no accessible metastatic lesion) in providing patients with advanced/metastatic solid tumors access molecular guided therapy and/or immunotherapy based on genomic results.
2. To describe the landscape of genomic alterations detected by reimbursed NGS
3. To describe he landscape of genomic alterations detected by comprehensive panel testing
4. To assess the technical success of comprehensive panel testing
5. To describe the uptake of treatments recommended by the molecular tumor board guided by the genomic testing.
Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
OTHER
NONE
Study Groups
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Foundation medicine NGS in parallel with local NGS
The patient will have in parallel FMI NGS test and Local reimbursed NGS test.
NGS testing
NGS test will be performed
Foundation Medicine NGS
The patient will have only FMI NGS test.
NGS testing
NGS test will be performed
LB Foundation Medicine NGS test
The patient do not have enough biopsy material or have tumor not accessible for a biopsy will have a liquid biopsy Foundation Medicine test.
NGS testing
NGS test will be performed
Interventions
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NGS testing
NGS test will be performed
Eligibility Criteria
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Inclusion Criteria
* 2- Patients with metastatic solid tumors that are candidates for systemic therapy (early lines are preferred). Numbers will be capped for frequent tumor types (breast cancer: 150 patients, NSCLC: 150 patients, colorectal cancer: 150 patients). There will be a cohort of 200 patients with rare tumors or tumors with rare histology (Eur. J. Cancer 2011; 47: 2493-2511). Patients will be recruited as they appear in clinical practice.
3- Patients will be enrolled following three clinical scenarios: a) patients eligible for local NGS testing (reimbursed or local practice); b) patients that are not eligible for reimbursed or local NGS testing; c) patients with no sufficient archival tissue meeting the pre-requirements will only undergo FMI liquid biopsy testing (exploratory cohort). That last cohort will be capped at 100 patients and will not have more than 50% of patients with the same tumor type.
4- Patients enrolled in scenario a) and b) must have enough tissue from a metastatic (preferred) or primary lesion biopsy for local testing and FMI testing. The tissue should not be more than 3 years-old and fixed in 10% neutral buffered formalin. Availability of metastatic biopsies performed after a previous therapy line are mandatory for patients treated with therapies that are known to induce acquired mechanisms of resistance (EGFR TKIs in NSCLC, aromatase inhibitors in breast cancer, TKIs in Gastrointestinal stromal tumor (GIST)…). Bone biopsies that undergo decalcification are not allowed.
5- Patient showing an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
6- Patients can only be enrolled if they are also concomitantly registered in the Precision 1 study and the investigator agrees to subsequent registration of genotype-driven treatments given and the investigator assessed outcome on these treatments (RR and PFS).
7- Patients able to provide written informed consent prior to enrollment into a potential subsequent clinical trial.
Exclusion Criteria
* 2- Inability to comply with protocol procedures.
* 3- Known presence of severe hematopoietic, renal, and/or hepatic dysfunction (according to the local PI).
4- - No informed consent provided.
* 5- Patient is not enrolled and followed as provided in Precision 1.
18 Years
ALL
No
Sponsors
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Foundation Medicine
INDUSTRY
Sciensano
OTHER_GOV
Roche Pharma AG
INDUSTRY
The Belgian Society of Medical Oncology
OTHER
Responsible Party
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Locations
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ZNA
Antwerp, , Belgium
GZA
Antwerp, , Belgium
AZ Klina
Brasschaat, , Belgium
Institute Jules Bordet
Brussels, , Belgium
AZ VUB
Brussels, , Belgium
Les Cliniques Universitaires St Luc
Brussels, , Belgium
Grand Hôpital de Charleroi
Charleroi, , Belgium
Universitaire Ziekenhuis Antwerpen
Edegem, , Belgium
UZ Gent
Ghent, , Belgium
Jessa Ziekenhuis
Hasselt, , Belgium
CHU Sart-Tilman
Liège, , Belgium
AZ Nikolaas
Sint-Niklaas, , Belgium
Countries
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Central Contacts
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Facility Contacts
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Abdelbari Baitar
Role: primary
Myriam Mertens
Role: backup
Jo Horemans
Role: primary
Charis Loos
Role: primary
Fanny Bustin
Role: primary
Sylvie Bartholomeus
Role: backup
Vanessa Fastenaekels
Role: primary
Malika Tahiri
Role: backup
Valérie Decroës
Role: primary
Stéphanie Warnon
Role: primary
Matthias Papier
Role: backup
Greet De Craen
Role: primary
Lore Vansteelant
Role: primary
Ann Tullen
Role: primary
Hélène Schroeder
Role: primary
Astrid Collinge
Role: backup
Other Identifiers
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BSMO2020-1
Identifier Type: -
Identifier Source: org_study_id