Clinical trial NCT02094742: BIG Molecular Screening Feasibility Study
Official title: The BIG Molecular Screening Feasibility Study:Testing the IT Infrastructure and Logistics of a Molecular Screening Program
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metastatic Breast Cancer
Keywords: screening program
metastatic breast cancer
molecular profile
gene sequencing
Lead sponsor: Jules Bordet Institute
Sponsor class: OTHER
Collaborators: name: Breast International Group
First posted: 2014-03-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent for all study procedures according to local regulatory requirements prior to enrollment into the study.
2. Age ≥ 18 years.
3. Histologically proven metastatic or locally recurrent invasive breast cancer.
4. Tumor tissue (FFPE and frozen) from recurrent or metastatic lesions available for research purposes.

Exclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) Performance Status \>2.
2. The biopsy procedure is estimated to be too risky for the patient.
3. Any bevacizumab treatment administered less than 3 weeks before new biopsy procedure.
4. No appropriate wash-out period for patients on anticoagulation therapy.

Primary outcomes:
measure: molecular screening program feasibility
timeFrame: 6 months after end of recruitment
Secondary outcomes:
measure: concordance of targeted gene mutation testing by different technologies
timeFrame: 6 months after end of recruitment
measure: number of patients with potential "actionable" mutations
timeFrame: 6 months after end of recruitment
measure: proportion of core biopsy specimens from invasive recurrent or metastatic lesions
timeFrame: 6 months after end of recruitment
measure: technical failure rate (FR)
timeFrame: 6 months after end of recruitment
measure: ability of the MSPP (IT platform) to sort patients to several simulated protocols
timeFrame: 6 months after end of recruitment
measure: ease of use of the MSPP
timeFrame: 6 months after end of recruitment
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Offenbach am Main
country: Germany
facility: Klinikum Offenbach
state: Frankfurt
city: Barcelona
country: Spain
facility: Val d'Hebron
city: Dundee
country: United Kingdom
facility: University Hospital
Study officials:
affiliation: Institut Jules Bordet, Brussels, Belgium
name: Sherene Loi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Jules Bordet, Brussels, Belgium
name: Christos Sotiriou, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Jules Bordet, Brussels, Belgium
name: Martine Piccart, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: