Clinical trial NCT03197805: Assessment of the Impact of RNA Genomic Profile on Treatment Decision-making in HER2 Equivocal Breast Cancer Patients
Official title: Prospective Study Assessing the Impact of RNA Genomic Profile Defined by a Genomic Test on Treatment Decision-making in Breast Cancer Patients With an ISH Equivocal HER2 Status- EQUIVOK Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Breast Cancer
Keywords: Equivocal Her 2
Genomic test
Lead sponsor: Centre Jean Perrin
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
name: NanoString Technologies, Inc.
First posted: 2017-06-23
Enrollment: 26
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Cohort longitudinal follow up
Primary purpose: DIAGNOSTIC

Brief summary: The American Society of Clinical Oncology (ASCO) and the /College of American Pathologists (CAP) recommend that HER2 status (negative or positive) must be determined in all patients with invasive breast cancer. The knowledge of HER2 status will help the oncologist in prescribing or not a HER2-targeted therapy to patients. Presently, two main methods are used to assess HER2 status: immunohistochemistry (IHC, protein expression) and in situ hybridization (ISH, gene expression) in order to classify tumor sample as positive, negative or equivocal. When a tumor is classified HER 2+ by IHC method, a second test is performed using ISH methods (FISH, SISH, CISH). In case of HER2 equivocal result with ISH method (4 ≤HER2 gene number copy \<6), the patient is eligible to an anti-HER2 therapy after discussed during MD-MM. This decision should be individualized on the basis of patient status (comorbidities and prognosis) and patient preferences after discussing available clinical evidence.

Based on molecular classification, RNA expression could help to discriminate breast cancer subtypes (luminal A, luminal B, HER2-overexpressed and triple negative). Prosigna is a genomic test, developed by NanoString® based on the PAM50 gene signature, which measures the expression of 50 genes to classify tumors into 1 of 4 intrinsic subtypes and could allow determining the HER2 status.

This study was designed in order to define if such a test could help the oncologist to define the better therapeutic decision in a HER2 equivocal population. In addition, concordance tests will be performed. The aim of this study is to assess the modification decision rate between the first and the second multidisciplinary decision-making meeting in HER2 equivocal patients using genomic testing.


Eligibility criteria: Inclusion Criteria:

* Performance status ≤ 2 (according to WHO criteria)
* Patient with early invasive breast cancer histologically confirmed stage I to IIIA)
* Positive or negative lymph node involvement
* Positive or negative Hormonal Receptors (Estrogens and/or Progesterone),
* Equivocal HER2 status (IHC Score 2 and equivocal ISH defined as HER2/Chr17 ratio \<2 and 4 ≤ HER2 gene number copy \< 6) as assessed on surgical specimen
* Adequate Hematological, Hepatic, Renal and Cardiac Functions
* Patient potentially eligible for an anti-HER2 therapy
* Patient eligible to receive an adjuvant therapy
* Signed Informed Consent
* Patient with social insurance.

Exclusion Criteria:

* Non-measurable tumor
* Unknown Hormonal Receptors
* Unknown node involvement
* Positive or negative HER2 status (Score 0, 1 or 3 IHC, or Negative or positive ISH)
* Disease stage ≥IIIB
* Patient not able to follow the trial.

Primary outcomes:
measure: The modification of therapeutical decision between the first and the second multidisciplinary decision-making meeting (MD-MM) using a genomic testing
timeFrame: The measure will be realised after the second multidisciplinary decision-making meeting that is about one month after patient's inclusion.
Secondary outcomes:
measure: The HER2 overexpression incidence according to RNA genomic profile among equivocal-HER2 patients
timeFrame: The measure will be done when the genomic test is realised, that is about three weeks after patient's inclusion.
measure: The concordance between the second multidisciplinary decision-making meeting decision and the HER2 genomic test result
timeFrame: The measure will be done when the genomic test is realised, that is about three weeks after patient's inclusion.
Other outcomes:
measure: To compare results from different ISH methods used
timeFrame: The measure will be done when the genomic test is realised, that is about three weeks after patient's inclusion..
measure: The concordance between local and centralized anatomopathologist HER2 status
timeFrame: The measure will be done when the genomic test is realised,that is about three weeks after patient's inclusion.
Locations:
city: Besançon
country: France
facility: CHRU Jean Minoz
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre François Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Grenoble
country: France
facility: CHU Albert Michalon
city: Limoges
country: France
facility: Hopital DUPUYTREN
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Institut de Cancérologie de Montpellier
city: Reims
country: France
facility: Institut Jean Godinot
city: Reims
country: France
facility: Institut du Cancer COURLANCY
city: Saint-Herblain
country: France
facility: Institut de Cancérologie de l'Ouest
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
Study officials:
affiliation: Centre Jean Perrin
name: Marie-Ange MOURET-REYNIER, MD
role: PRINCIPAL_INVESTIGATOR
References: