Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All patients will undergo a biopsy of their metastatic lesion and have a blood sample taken for molecular screening purposes. No drugs are administered or other interventions are performed.

biopsy

Sherene Loi, MD, PhD

Christos Sotiriou, MD, PhD

Martine Piccart, MD, PhD

This pilot study examines the feasibility and turnaround time of performing and obtaining data from a few key molecular assays. These assays will be performed using different laboratories and technologies from core biopsies taken from patients diagnosed with invasive recurrent or metastatic breast cancer. All results will be uploaded, stored and assessed using the IT Molecular Screening Prototype Platform (MSPP). The MSPP will also be evaluated for ease of use to screen patients for participation in future molecularly defined clinical trials in breast cancer.

This study will accept patients with metastatic/recurrent breast cancer disease. The core biopsies must be taken from a metastatic lesion. To note, these patients can be biopsied at any phase of their metastatic disease (at diagnosis, at progression etc).

* The patient will sign a specific Informed Consent Form (ICF).
* The Investigator will access the MSPP, register the patient and enter basic patient clinical data necessary for the verification of the eligibility criteria.
* The patient will prospectively undergo invasive recurrent or metastatic lesions (1 site easily accessible, such as skin, lymph node or liver) core biopsies including the collection of tumor samples consisting of 2 Formalin Fixed Paraffin Embedded (FFPE) Tissues and 1 (2 recommended) fresh frozen samples embedded in Optimal Cutting Temperature (OCT) compound or stored in RNAlater. One whole blood sample (1x10mL) will also be collected.
* The Investigator will record the biological samples via the MSPP bio-tracking system
* The Investigator is responsible for the immediate dispatch of the samples to the designated central laboratories.
* The assays will be performed at the central laboratories. It should be noted that:

  * Two FFPE samples will be sent to IEO, Milan, Italy. One FFPE sample will be stored. The second FFPE will be used to perform pathological tests. The tests include ER, HER2, Ki67 and PTEN status evaluation by immunohistochemistry (IHC) and FISH (for HER2 only); and of PIK3CA hot spot somatic mutations identification by Sanger DNA sequencing. Unstained sections (10x5µm) and extracted DNA, taken from the FFPE tissue core used for the testing, will be sent to IPG and Sanger, respectively, by the central laboratory.
  * The assays performed at IPG and Sanger will consist of targeted breast cancer genes mutations identification by Ion Proton or HiSeq 2000 DNA sequencing respectively. To note, targeted genes screen will also be coupled with identification of other substitutions, short indels and copy number variants (CNVs).
  * One fresh frozen sample embedded in OCT or stored in RNAlater will be sent to IJBordet, Brussels, Belgium, together with the blood sample, for Affymetrix gene expression profiling and for chromosomal and SNP-analysis using the Cytoscan platform (Affymetrix). The blood sample will be stored.
* The central laboratories will upload the processed data that is generated as a result of the central testing onto the MSPP.
* An alert, by e-mail, will be sent to the Investigator when the central results are available. The Investigator will log on to MSPP and obtain the results.
* The residual biological samples and derivatives will be stored in the BIG study Repository for 15 years or the maximum allowed by local regulations whichever is the shortest. If needed, remaining material will be used for future research as high throughput genetic analysis.

It should be noted that the results obtained from the BIG Molecular Screening Feasibility Study will NOT be used for treatment decision-making. Patients should receive anti-cancer therapy as per the patient's treating physicians decision and in accordance with local institutional guidelines. There is no planned follow-up period. The trial will end after all the information from the 30 accrued patients is entered into the MSPP, within a maximum of 2 months after the recruitment of the last patient.

BIG Molecular Screening Feasibility Study

The BIG Molecular Screening Feasibility Study:Testing the IT Infrastructure and Logistics of a Molecular Screening Program

To evaluate the feasibility of implementing a molecular screening program in order to identify molecular traits in patients that may render them eligible for clinical trials using specific targeted agents.

To test the concordance of targeted breast cancer genes mutations testing by different technologies: Life technologies Ion Proton Sequencer (by IPG) versus Illumina Hiseq 2000 (by Sanger).

To evaluate how many of these patients have potential "actionable" mutations that could theoretically render them eligible for the current active targeted trials using FDA approved drugs (as per www.clinicaltrials.gov).

To determine the proportion of core biopsy specimens obtained from invasive recurrent or metastatic lesions from which adequate amounts of high quality DNA and RNA can be extracted.

To evaluate the technical failure rate (FR) for every single tests (ER, HER2, KI67, PTEN, GEP, CNV and targeted genes screen) using core biopsies.

To evaluate the ability of the MSPP (IT platform) to sort patients to several simulated protocols based on pathological and molecular tests results.

To evaluate the ease of use of the MSPP (IT platform)

Breast International Group

Jules Bordet Institute

Blood and Lymph Conditions

Rare Diseases

Leukemia

Myeloproliferative Disorders

Thrombocytosis

Bone Marrow Diseases

Hematologic Diseases

Chronic Myeloproliferative Disorders

Next generation sequencing of candidate genes (JAK2, cMPL, CALR, ASXL1 and NF-E2)

Gene sequencing

Serge Carillo

The MPL gene is implicated in two groups of hematological pathologies: congenital amegakaryocytic thrombocytopenia (CAMT) and Phi negative myeloproliferative neoplasia (MPN). Fifty germline mutations have been identified in CAMT, yet only a dozen activating mutations have been described in MPN. Most are somatic, distributed mainly in the transmembrane (TM) and juxtamembrane (JM) domains. However, a few rare germline mutations located in the extracellular domain (ECD) have also been reported: K39N, R102P and P106L.

Next generation sequencing technology has been used to study the complete MPL gene, identifying numerous variants, most of unknown significance. The study investigators have a series comprising 41 variants of unknown significance, whose allelic frequencies suggest a germline origin for 80% of them. Their distribution within the MPL gene is similar to that of inactivating mutations, except that they were discovered in the context of suspected myeloproliferative disease. Characterizing the activity of these variants would confirm the diagnosis of MPN, opening the door to specific treatment (cytoreductive, JAK2 inhibitor or interferon). It also has an important prognostic value, particularly in the case of MPN, for which life expectancy varies from 5 to 7 years, with terminal progression to acute myeloid leukemia (AML in 15 to 20% of cases) or bone marrow failure.

Using a battery of functional assays, this study aims to characterize these variants.

Blood samples and bone marrow samples will be taken depending on the clinical management of the patient

Functional Characterization of Thrombopoietin/cMPL Receptor Mutations in Myeloproliferative Neoplasia

Western blot of JAK2, STAT (3 and 5) AKT, ERK1 /2 proteins

Centre Hospitalier Universitaire de Nīmes

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Familial Colorectal Cancer

Participants belong to a family with increased risk for CRC, will be analyzed with gene sequencing

Gene sequencing by exome capture and high throughput sequencing for identification of rare variants

gene sequencing

Finn Drabløs, PhD/Prof

The project will use exome sequencing to search for genetic predispositions for familial colorectal cancer (CRC). Except for certain syndromes there is today no good method for identifying individuals with a hereditary high risk for CRC (about 25% of the cases). There is currently no routine screening of the population in Norway for CRC today. Coloscopy, which is the most reliable method, is demanding with respect to resources, it can be painful, and may have complications. This project will attempt to find genetic determinants for identification of individuals with increased risk for familial CRC. Such methods will reduce unnecessary medical examination of unaffected family members, and will make it easier to focus health services on individuals with increased risk. This will represent a significant contribution towards improved health reduced death rate caused by CRC. The project includes research on the ethical aspects, in particular challenges related to how feedback to donors is handled.

Participants will be from a specific family, and will be selected by invitation to volunteer.

Sequencing to Identify Gene Variants in Familial Colorectal Cancer

Exom-sekvensering for å Identifisere høyrisiko Genvarianter i en Familie Predisponert for Colorectal Cancer

For each participant the genome will be analyzed by exome capture and high throughput sequencing. The exome data will be compared between participants and to reference data for identification of unique variants that can be associated with disease risk.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
BIG Molecular Screening Feasibility Study	NCT02094742	Metastatic Brea...	biopsy	18 Years -	Jules Bordet Institute
Functional Characterization of Thrombopoietin/cMPL Receptor Mutations in Myeloproliferative Neoplasia	NCT06246006	Myeloproliferat...	Gene sequencing	18 Years - 99 Years	Centre Hospitalier Universitaire de Nīmes
Sequencing to Identify Gene Variants in Familial Colorectal Cancer	NCT01904630	Colorectal Canc...	gene sequencing	20 Years -	Norwegian University of Science and Technology
Sequencing to Identify Gene Variants in Familial Colorectal Cancer	NCT01904630	Colorectal Canc...	gene sequencing	20 Years -	Norwegian University of Science and Technology
Functional Characterization of Thrombopoietin/cMPL Receptor Mutations in Myeloproliferative Neoplasia	NCT06246006	Myeloproliferat...	Gene sequencing	18 Years - 99 Years	Centre Hospitalier Universitaire de Nīmes

Spots Global Cancer Trial Database for gene sequencing