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

Patients with advanced refractory solid tumors receive personalized therapy with the guidance of Molecular Tumor Board after the NGS(next generation sequencing).

This study is to observe this therapy model outcomes

Personalized therapy model with Molecular Tumor Board and Next Generation Sequencing

Haitao Wang

This study seeks to evaluate the clinical value of the personalized therapy model with the guidance of Molecular Tumor Board (MTB) after Next Generation Sequencing(NGS), and to track patient outcomes.

This is a study from the real world. Advanced refractory solid tumors patients with no standard treatment options have a very poor prognosis. In recent years, the application of s Next Generation Sequencing (NGS) has rapidly expanded the breadth and depth of understanding of the molecular mechanism of tumors, laying a foundation for the development of precision medicine for tumors. Researchers can build a molecular phenotype of advanced refractory solid tumors by NGS. Some retrospective study shows that Molecular Tumor Board (MTB) therapy model brings therapeutic hope. So, investigators hope that this therapy model combined with NGS may provide treatment recommendations for advanced refractory solid tumors patients. Those recommendations may include some off-label targeted therapies. This study seeks to evaluate the clinical value of the personalized therapy model with the guidance of MTB after NGS, and to track patient outcomes, including ORR (Objective Response Rate), PFS (Progression Free Survival), OS (Overall Survival) and ADR (Adverse Drug Reaction).

Personalized Therapy of Molecular Tumor Board Participation With the Guidance of Next Generation Sequencing

Prospective and Retrospective Register Study of Personalized Therapy of Molecular Tumor Board Participation With The Guidance of Next Generation Sequencing

ORR is the percentage of participants with best overall response of complete response (CR), partial response (PR). Response categories: CR, PR, SD (stable disease), PD (progressive disease) Criteria on which physicians determined therapy response also will be captured by using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 to evaluate.

Progression-free survival (PFS) is defined as progression free survival of all the evaluable participants who receive targeted drug therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1).

OS is defined as time from initiation to death of any cause.

Adverse events determined according to CTCAE (version 4.03).

Tianjin Medical University Second Hospital

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Patients with metastatic prostate cancer in disease progression or not receiving active systemic therapy will undergo a liquid biopsy

Liquid Biopsy

Patients will be prompted to request an archival tumor sample from metastatic origin (preferably) and to send it to the central laboratory for analysis

Archival Tumor DNA sequencing

HOPE-Prostate Study Team

HOPE Prostate is an observational study that aims at promoting research against metastatic prostate cancer by means of collective research led by patients (patient-centric trial). Patients with metastatic prostate cancer living in Spain will voluntarily register and fulfil their journey in the study through the study's digital tool. Mainly they are prompted to answer questionnaires about their disease, and to provide a blood sample and an archival tumor biopsy. In HOPE Prostate these samples will be genomically analyzed and every patient case will be presented in a multidisciplinary molecular advisory board (MAB). The MAB will issue a plain report explaining the significance of the results and will try to enumerate future therapeutic options that match patient history and his genomic profile. Finally, patients will have to answer short follow-up questionnaires twice a year for 3 years.

The study data will allow us to advance implementing precision medicine to improve the management of current and specially future metastatic prostate cancer patients.

HOPE PROSTATE - SOLTI-2102 is a national, prospective, real-world clinical practice study for patients diagnosed with metastatic prostate cancer (mPC) who are about to receive, or receiving, or completed treatment for advanced disease under standard clinical practice conditions, regardless of where they are receiving their medical care (academics vs community practices).

Patients will lead their own inclusion and, participation, and self-provide follow-up data in the study through a digital tool that will guide them in every step of the journey. The digital tool will collect general patient characteristics and demographics data, informed consent, disease characteristics, diagnostic tools employed along their oncological history, sample collection dates (for tissue,blood and saliva), genetics and tumor mutations, treatment history, patient's expectations and perceptions with regards to the process of undergoing genomic tumor testing and clinical trial experience from patients living with mPC. Moreover, when patients involve their physicians, they will receive notifications from the platform with molecular reports and an invitation to participate in the periodic Molecular Advisory Boards of the study (MAB).

The study will be in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines and applicable regulatory requirements. Approval of the study protocol will be from an Independent Ethics Committee (IEC).

Patients will request to participate in HOPE-PROSTATE through the study website and a personal session in the digital tool, will be created. Then:

* In a short inclusion questionnaire patients will introduce some demographic and medical data, and if available, medical reports.
* A medical monitor will validate that the inclusion and exclusion criteria are met and will contact patients to explain the study procedures, objectives and answer questions.
* Upon validation, patients will be contacted through the digital tool to give their informed consent or alternatively in paper (at a partner local laboratory).
* After informed consent validation, the digital tool will inform them of the steps to follow to proceed with their patient journey.
* Patients will fill out a short questionnaire to assess their pre-test expectations with regards to anticipated implications of testing and motivations to undergo testing.
* Before results obtention, patients will be required to complete a more extensive questionnaire about their medical history to use it at the Molecular Advisory Board (MAB) meeting.

An information letter will be sent to all patients to be forwarded to their treating physician to be aware of the HOPE-PROSTATE study objectives. Moreover, upon patient's consent, treating physicians will be invited to be registered in a database to be aware of testing progress, receive molecular results and participate in the periodic MAB.

Upon inclusion, patients will be instructed through the digital tool to attend the closest local partner laboratory to perform the necessary blood draw at an appropriate time. In addition, a letter to request the most recent tumor tissue sample at his hospital will be provided; we anticipate collecting tumor tissue samples from at least 80 included patients.

At partner local laboratory:

* Patient may have the possibility to sign the paper study Informed Consent Form if digital signature is not possible.
* Blood samples will be collected (at the time of disease progression).
* Patients will hand over their tumor blocks, previously collected from the local hospitals. At the same time, a saliva sample will be collected.

At the time of documented disease progression and before the initiation of a subsequent line of therapy, patients will be instructed to contact SOLTI to organize their blood sample collection at the closest venue of the partner laboratory. The sample will be sent to the GuardantHealth central laboratory in Redwood City, California. A second blood sample from the same extraction will be shipped to the study central laboratory at Vall d'Hebron Institute of Oncology (VHIO) for complementary analyses.

While we anticipate most mPC patients would join the study in the castration-resistant setting, we plan for a subgroup analysis among patients who join the study at first diagnosis of metastatic, hormone-naïve disease. Patients with metastatic hormone-naïve disease will be included if the blood sample can be collected within 4 weeks from the start of luteinizing hormone releasing hormone antagonist (LHRHa) therapy, although ideally the sample should be collected even before LHRHa initiation. After enrolling 30 hormone-naïve disease patients, we will conduct a feasibility analysis based on the circulating tumor DNA (ctDNA) detection rate (considering an expected detection rate above 80%). If this approach is feasible, the subgroup of patients with metastatic hormone-naïve disease will continue to recruit up to a maximum of 100 patients.

Samples will undergo plasma-based Next Generation Sequencing panel using the "GuardantOMNI" panel test which is a diagnostic system based on the sequencing of 500 genes, as well as the determination of biomarkers that include microsatellite instability (MSI), tumoral mutational burden (TMB) and Homologous Recombination Deficiency (HRD) score. Molecular reports will be generated and sent to the patient physician (if involved), then these data will be discussed at the MAB and a MAB report with molecular data interpretation and a therapeutic recommendation (if there is any) will be send to the patient.

In certain populations of special interest, a repeated ctDNA analysis at a later timepoint will be considered after the MAB evaluation:

* Patients with BRCA gene or HRD pathway alterations who have undergone the test before targeted treatment and develop secondary resistance to PARP inhibitors.
* Patients who have undergone ctDNA prior to exposure to both docetaxel and androgen receptor-targeted agents (ARTA) (SoC Treatments) will be invited to be tested again after progression to these SoC agents to determine the possibility of discovering new therapeutic targets.

At least 80 tumor tissue samples from archival core biopsies or surgical specimens preferably metastatic will undergo genomic characterization. Samples will be sent by participating patients or through treating institutions upon patient's request.

Formaline-fixed paraffin embeeded (FFPE) blocks will be assessed at VHIO by a pathologist and H\&E slides will be digitalized. Samples with sufficient tumor content will undergo DNA extraction, quantification and quality control. The obtained DNA will be divided for two downstream applications:

1. All samples will undergo targeted sequencing using a previously validated capture-based panel including \>400 genes (mutations, Copy Number Alterations, TMB) at VHIO laboratories and a genomics report will be generated.
2. For those samples with enough DNA quality and quantity after completing the study related targeted sequencing, remaining DNA will be used for retrospective whole exome or whole-genome sequencing (WGS) analysis using modified protocols optimized for FFPE samples for exploratory comparative analysis .

Patients will always have the possibility of getting their treating physician involved in their study participation at any point along the journey which will be recommend by the sponsor. Physicians will be invited to register in a database to inform them most efficiently. They will receive the molecular reports generated and will be invited to participate in the periodic MAB periodic meetings. When the patient case is presented, they will have the opportunity to do so. An informative letter will be provided to all patients so they can share it with their doctors at the time of inclusion.

Besides the study per se, HOPE PROSTATE-SOLTI-2102 educational program for Health Care Professionals (HCP) will focus on physicians treating mPC although their patients participate or not in the investigational part of the study. The two main educational initiatives will be: the Molecular Advisory Board (MAB) meetings and the Initial Educational Meeting.

Upon genomics data availability, patients will have the possibility to update their medical history record through a questionnaire in the platform. Using mPC patient clinical and molecular data a SOLTI dedicated team will prepare the periodic MAB meetings to discuss the cases with new genomics reports available to highlight the potential Scientific relevance of the molecular findings according to patient's clinical progression and discuss potential targeted therapies that could fit each of the cases. The MAB will complement the genomic reports with a text summarizing their interpretation of the results and if possible, the potential future therapeutic strategies that could be considered according to patient profile. We aim at generating a space where mPC HCP can learn about the emerging strategies in mPC management, how to interpret genomics data and embrace a fruitful debate to promote continuous learning about molecular alterations and training on how to use the newly available tools in the clinics. MAB meetings will be scheduled once or twice a month and when possible: they will be complemented with brief educational lectures addressing relevant hot topics in PC management.

Three months after the MAB final report is sent, patients would fill out a second questionnaire to notify if the information received was relevant for subsequent treatment decisions. Moreover, they will be required to fill out the questionnaire to assess the fulfillment of their previous expectations.

This Board will be constituted by a multidisciplinary group of experts in PC clinical management (including medical oncologists, urologists and radiation oncologist), cancer genetics, cancer genomics, bioethics, and pathology. The board aims to be representative of the diversity in our country for managing prostate cancer patients. Besides permanent MAB members, physicians treating HOPE PROSTATE study participants will be invited to participate in the discussions about their patients. Moreover, SOLTI will disseminate the MAB meetings, allowing the free attendance of interested HCP from across the nation. With the aim of promoting participation among nation-wide physicians, these meeting will be held in Spanish and using an online platform.

Irrespective of the MAB outcome, all patients' clinical evolutions will be followed. Patients will be asked to self-report follow-up data every 6 months to determine the status of their disease through the digital tool for at least three years.

To reaffirm the patients-centric approach of HOPE PROSTATE-SOLTI-2102, the study will be complemented by a patient empowerment program that will include informative digital video-capsules and video tutorials about precision medicine and the HOPE Prostate project itself. The content from the digital workshop sessions will be available online and the videos will be public and accessible through the study website to facilitate access to information.

Understanding the patient experience is key to deliver patient-centered care. By looking at various aspects of the patient experience (expectations, concerns, attitudes, and knowledge), we aim at improving healthcare respecting the individual patient's preferences, needs and values.

Before pursuing the genomic test, patients will be invited to complete a series of questionnaires (adapted from previous studies), focused on patients' knowledge about genomic testing and their concerns and expectations around how genomic testing may impact the treatment selection and disease managements9. Three months after MAB report delivery, the same questionnaires will be repeated to evaluate the fulfillment of their previous expectations and the overall experience of the patient participating in the study. After this initial post-recommendation questionnaire, shorter follow up questionnaires will be displayed every six months for three years.

Blood sample collection and archival tumor tissue collection

Feasibility and Impact of Liquid Biopsy Genomic Profiling on Treatment Patients With Metastatic Prostate Cancer in Spain (SOLTI-2102)

Real World Clinical Practice Study to Assess the Feasibility and Impact of Liquid Biopsy-based Genomic Profiling on Treatment Decision Making for Patients With Metastatic Prostate Cancer in Spain (SOLTI-2102)

Percentage of patients for whom a liquid biopsy result can be obtained.

Proportion of patients with a putatively targetable (ESCAT levels I-III) alteration detected.

Frequency of PC gene mutations in the study population including DNA repair pathways (BRC1/2 inactivating mutations, etc.), genes associated with phosphatidylinositol-3 kinase (PI3K) and cell cycle regulation pathways and others.

ctDNA detection rate in hormone-naïve and castration-resistant mPC.

* Concordance between ctDNA mutation status and tissue mutation status (specially in Homologous Recombination Repair and other clinically relevant genes).
* Concordance between ctDNA and tissue TMB calculations.
* Concordance between ctDNA and tissue Variant Allelle Frequency for given mutations.

Percentage of patients who received a matched therapy against an alteration detected by ctDNA and/or tissue targeted sequencing during the follow-up period.

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
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
Personalized Therapy of Molecular Tumor Board Participation With the Guidance of Next Generation Sequencing	NCT03929653	Solid Tumor, Ad...	Personalized th...	18 Years -	Tianjin Medical University Second Hospital
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
Feasibility and Impact of Liquid Biopsy Genomic Profiling on Treatment Patients With Metastatic Prostate Cancer in Spain (SOLTI-2102)	NCT05885009	Metastatic Pros...	Liquid Biopsy Archival Tumor ...	18 Years -	SOLTI Breast Cancer Research Group

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