Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

All Drugs and Chemicals

Immunomodulating Agents

Comprehensive genomic profiling

Brigitte Maes, Dr

Gordana Raicevic Toungouz

Max Schreuer

Joke van Gaelen

Joanna Vermeij, Dr

Jo Horemans

Annemie Rutten, Dr

Lies Pottel

Jacques Van Huysse

Vanessa Fastenaekels

Malika Tahiri

Lore Decoster, Dr

Stéphanie Warnon

Jean-Luc Canon, Dr

Julia Lenaerts

Hans Prenen, Dr

Lore Vansteelant

Sylvie Rottey, Prof. Dr

Ann Tullen

Jeroen Mebis, Prof. Dr

Isabelle Vanden Bempt

Sabine Tejpar, Prof. Dr

Sophie Adriaens

Francesca Dedeurwaerdere, Dr

Lynn Decoster

Lynn Decoster, Dr

The project, called "BALLETT" (Belgian Approach of Local Laboratory Extensive Tumor Testing), has a double goal: (1) show the relevance of broad molecular profiling to improve oncological patients care, (2) demonstrate that broad molecular testing can be performed in a decentralized setting by local diagnostics laboratories in a fully standardized and uniform way while complying with the highest quality standards.

This 2-year study involves the consortium of 9 cooperating Belgian NGS laboratories and will enroll 936 metastatic or locally advanced cancer patients coming from 13 different Belgian hospitals and cancer centers. Upon inclusion, all cancer patients will be offered 'comprehensive genomic profiling' (CGP) using Illumina's TSO500 NGS panel. This targeted NGS panel of 523 genes allows for the detection of single nucleotide variants, small indels, copy number variations and fusions, as well as for the determination of the 'tumor mutational burden' (TMB) and the 'microsatellite-instability' status (MSI). Both the wet lab execution of the CGP as well as the biological and clinical classification of the variants will be performed in a fully standardized way among the 9 participating Belgian local NGS laboratories.

The CGP results will be interpreted and discussed in the weekly meeting of the BALLETT national molecular tumor board (MTB), composed of oncologists, pathologists, molecular biologists, geneticists and bioinformaticians. The MTB will provide recommendations for targeted or immunotherapy based on the CGP results. Clinical Decision Support platforms OncoKDM (OncoDNA) and Clinical Genomics Workspace (PierianDx), both expert software that turns NGS data into actionable clinical information, will be used. The resulting therapy recommendation may consist of an approved therapy, a clinical trial, a medical need program or off-label use of cancer drugs. Treating physicians will receive the MTB recommendations and decide on the actual management of their patients. Reasons for not following the MTB recommendation will be registered.

The objectives of the project are:

1. To evaluate the clinical value of CGP in "real-world" practice in giving patients with advanced/metastatic solid tumours broader access to precision medicine
2. To describe the landscape of genomic alterations and quantify the actionable variants detected by comprehensive panel testing
3. To evaluate the number of actionable variants that would have been missed if the NGS analysis was limited to the reimbursed NGS panel (ComPerMed panel).
4. To assess the technical success of CGP
5. To standardize CGP data analysis, clinical interpretation, therapy recommendation and reporting among participating laboratories to the highest extent possible
6. To describe and to quantify the uptake of treatments and the inclusion in clinical trials recommended by the molecular tumour board guided by the CGP
7. To assess clinical benefit by calculating PFS ratio for individual patients (PFS on CGP-selected therapy/PFS on prior therapy) (null hypothesis: ≤ 15% of patient population has PFS ratio of ≥ 1.3)
8. To work in a multi-stakeholder approach to attract more innovative treatments and clinical trials in Belgium
9. To establish a Belgian genomic tumor database under the authority of the governmental 'Sciensano' thereby increasing public health knowledge in Belgium

A Study to Examine the Clinical Value of Comprehensive Genomic Profiling Performed by Belgian NGS Laboratories: a Belgian Precision Study of the BSMO in Collaboration With the Cancer Centre

A Study to Examine the Clinical Value of Comprehensive Genomic Profiling Performed by Belgian NGS Laboratories: a Belgian Precision Study of the BSMO in Collaboration With the Cancer Centre - Belgian Approach for Local Laboratory Extensive Tumor Testing (BALLETT)

Number/prevalence of variants with a classification of clinical significance Tier 1A or 1B (strong clinical significance) and Tier 2C and 2D (potential clinical significance) using CGP versus local NGS testing (if available) and/or versus minimally required ComPerMed panel.

Tiering according to Li et al. AMP/ASCO/CAP. J Mol Diagn 19:4-23, 2017.

Percentage of patients with MTB recommendation categorized according to variant-therapy match scoring system, percentage of patients accessing genotype-informed treatment, turnaround time from CGP request to MTB recommendation, proportion of patients accessing molecular guided therapy or immune checkpoint inhibitors or combinations based on the result of CGP, timing of treatment initiation following MTB recommendation, proportion of deviations from treatment recommendations and reasons (rapid clinical deterioration, other protocol, patient ineligible, off-label treatment unavailable, clinical trial not feasible (e.g. physical distance), clinical trial not recruiting, physician's decision, patient's choice, ...)

PFS based on RECIST 1.1 evaluation of patients on the CGP recommended therapy and PFS ratio (PFS on CGP-selected therapy/PFS on prior therapy) (null hypothesis: ≤ 15% of patient population has PFS ratio of ≥ 1.3)

Including cost calculation and reimbursement data to support economic analysis (microcosting from the lab perspective and budget impact from the payer's perspective).

Illumina, Inc.

OncoDNA

PierianDx

The Belgian Society of Medical Oncology

Rare Diseases

Cholangiocarcinoma

Neoplasms, Unknown Primary

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Eligible patients that present with Cholangiocarcinoma.

Eligible patients with cancer of unknown primary site (CUP).

Eligible patients that meet the definition of rare cancers (incidence of less than 6 per 100,000 in the United States).

Eligible patients will have Foundation Medicine blood and tissue testing and have their results reviewed by the study's Virtual Molecular Tumor Board which, in turn, will make recommendations for treatment to treating physicians.

FoundationOne CDx and FoundationOne Liquid CDx

Mary Oster

Shumei Kato, M.D

Razelle Kurzrock, M.D.

Vivek Subbiah, M.D.

Shumei Kato, M.D.

This open label, non-randomized, multi-center, pragmatic study aims to establish whether patients with rare tumors can benefit from matched molecular therapy as dictated by their next-generation sequencing (NGS) results.

This open label, non-randomized, multi-center, pragmatic study aims to establish whether patients with rare tumors can benefit from matched molecular therapy as dictated by their next-generation sequencing (NGS) results. The study leverages a remote consent and participation approach to open enrollment to all patients with rare tumors within the United States. Traditional, site-based patient consenting and participation is also available for enrollment to the study.

Each participant will undergo comprehensive genomic profiling (CGP) by Foundation Medicine Inc. (FMI) of their tumor as well as plasma circulating cell-free DNA. Plasma circulating cell-free DNA may be additionally collected for repeat CGP at various timepoints during the study.

The CGP findings will be provided by FMI directly to the treating physician and study sponsor TargetCancer Foundation (TCF), with TCF presenting cases with genomic findings to the Virtual Molecular Tumor Board (VMTB). The VMTB will analyze the findings and provide a written report to the treating physician on recommended treatments and/or relevant clinical trials; the treating physician makes all treatment decisions. The resultant treatments and treatment responses will be tracked longitudinally during the term of this study, thus linking molecularly informed treatments to specific patient outcomes.

TCF-001 TRACK (Target Rare Cancer Knowledge) Study

The primary feasibility endpoint is the percent of participants who receive a molecularly targeted matched treatment after recommendation from the VMTB. Point estimates and confidence interval estimations will be calculated for percent of participants on matched treatments.

The primary efficacy endpoint is the progression-free survival (PFS) among participants who received the molecularly targeted matched treatment. Kaplan-Meier estimates will be constructed for time-to-event endpoints, including progression-free survival (PFS). Cox regression analysis will be applied to model PFS by putative covariates such as performance status, type of tumor, prior lines of treatment, and whether matched treatments are received.

Tumor molecular profiles will be correlated to treatment outcome, assessed by measures including the response rate, the rate of stable disease (SD)\>6 months/partial response (PR)/complete response (CR), progression-free survival (PFS), PFS ratio (comparison of the PFS used after molecular profiling to PFS on prior treatment), time to treatment failure, and overall survival. Kaplan-Meier estimates will be constructed for time-to-event endpoints, including overall survival (OS).

Foundation Medicine

TargetCancer Foundation

Blood and Lymph Conditions

Immune System Diseases

Behaviors and Mental Disorders

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Hematologic Neoplasms

Aggression

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Lymphosarcoma

Peripheral T-cell Lymphoma

Acute Graft Versus Host Disease

High-throughput image based in-vitro drug screening on primary patient tumor cells

Next generation functional drug screening

Comprehensive targeted profiling of genetic aberrations on primary patient tumor material

Philipp B. Staber, MD, PhD

EXALT-2 is a prospective, randomized, three arm study for treatment decision guided either by either comprehensive genomic profiling, next generation drug screening or physician's choice

Comprehensive Genomic Profiling and Next Generation Functional Drug Screening for Patients With Aggressive Haematological Malignancies

Comprehensive Genomic Profiling and Next Generation Functional Drug Screening for Patients With Aggressive Haematological Malignancies: Next Generation Personal Hematology

The study aims to identify if next-generation functional drug screening (ngFDS) and/or comprehensive genomic profiling (CGP; FoundationOne®Heme) compared to physicians' choice guided treatment will have an increased percentage of patients with a ratio

≥1.3 of progression free survival (PFS)/PFS of most recent treatment in patients with aggressive haematological malignancies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Examine the Clinical Value of Comprehensive Genomic Profiling Performed by Belgian NGS Laboratories: a Belgian Precision Study of the BSMO in Collaboration With the Cancer Centre	NCT05058937	Solid Tumor Metastatic Canc...	Comprehensive g...	18 Years -	The Belgian Society of Medical Oncology
TCF-001 TRACK (Target Rare Cancer Knowledge) Study	NCT04504604	Rare Cancers Cholangiocarcin... Cancer of Unkno...	FoundationOne C...	18 Years -	TargetCancer Foundation
Comprehensive Genomic Profiling and Next Generation Functional Drug Screening for Patients With Aggressive Haematological Malignancies	NCT04470947	Advanced Lympho... Refractory Lymp... Refractory Leuk... Refractory Acut... Refractory T-Ce...	Next generation... Comprehensive g...	18 Years -	Medical University of Vienna
TCF-001 TRACK (Target Rare Cancer Knowledge) Study	NCT04504604	Rare Cancers Cholangiocarcin... Cancer of Unkno...	FoundationOne C...	18 Years -	TargetCancer Foundation
TCF-001 TRACK (Target Rare Cancer Knowledge) Study	NCT04504604	Rare Cancers Cholangiocarcin... Cancer of Unkno...	FoundationOne C...	18 Years -	TargetCancer Foundation
Comprehensive Genomic Profiling and Next Generation Functional Drug Screening for Patients With Aggressive Haematological Malignancies	NCT04470947	Advanced Lympho... Refractory Lymp... Refractory Leuk... Refractory Acut... Refractory T-Ce...	Next generation... Comprehensive g...	18 Years -	Medical University of Vienna
TCF-001 TRACK (Target Rare Cancer Knowledge) Study	NCT04504604	Rare Cancers Cholangiocarcin... Cancer of Unkno...	FoundationOne C...	18 Years -	TargetCancer Foundation
A Study to Examine the Clinical Value of Comprehensive Genomic Profiling Performed by Belgian NGS Laboratories: a Belgian Precision Study of the BSMO in Collaboration With the Cancer Centre	NCT05058937	Solid Tumor Metastatic Canc...	Comprehensive g...	18 Years -	The Belgian Society of Medical Oncology

Spots Global Cancer Trial Database for comprehensive genomic profiling