Assessment of the Impact of RNA Genomic Profile on Treatment Decision-making in HER2 Equivocal Breast Cancer Patients (EQUIVOK)

July 24, 2019 updated by: Centre Jean Perrin

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Besançon, France, 25030
        • CHRU Jean Minoz
      • Bordeaux, France, 33076
        • Institut Bergonié
      • Caen, France, 14000
        • Centre François Baclesse
      • Clermont-Ferrand, France, 63000
        • Centre Jean Perrin
      • Dijon, France, 21079
        • Centre Georges François Leclerc
      • Grenoble, France, 38043
        • CHU Albert Michalon
      • Limoges, France, 87042
        • Hôpital Dupuytren
      • Lyon, France, 69373
        • Centre léon bérard
      • Marseille, France, 13009
        • Institut Paoli Calmettes
      • Montpellier, France, 34298
        • Institut de Cancérologie de Montpellier
      • Reims, France, 51056
        • Institut Jean Godinot
      • Reims, France, 51100
        • Institut du Cancer Courlancy
      • Saint-Herblain, France, 44805
        • Institut de Cancérologie de l'Ouest
      • Strasbourg, France, 67065
        • Centre Paul Strauss
      • Toulouse, France, 31059
        • Institut Claudius Regaud
      • Vandœuvre-lès-Nancy, France, 54519
        • Institut de Cancerologie de Lorraine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Use of PAM 50 test in Her2 equivocal breast cancer patient
Patients with an equivocal-HER2 breast cancer (IHC Score 2 and equivocal ISH defined as HER2/Chr17 ratio <2 and 4 ≤HER2 gene number copy < 6) will be eligible for RNA genomic test (PAM 50 test).
Diagnostic test: PAM 50 test
Patients with an equivocal-HER2 breast cancer (IHC Score 2 and equivocal ISH defined as HER2/Chr17 ratio <2 and 4 ≤HER2 gene number copy < 6) will be eligible for RNA genomic test (PAM 50 test). The use of genomic test could help the oncologist to define the better therapeutic decision in a HER2 equivocal population.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The modification of therapeutical decision between the first and the second multidisciplinary decision-making meeting (MD-MM) using a genomic testing
Time Frame: The measure will be realised after the second multidisciplinary decision-making meeting that is about one month after patient's inclusion.
Percentage of therapeutical strategy changes between the first and the second multidisciplinary decision-making meetings.
The measure will be realised after the second multidisciplinary decision-making meeting that is about one month after patient's inclusion.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The HER2 overexpression incidence according to RNA genomic profile among equivocal-HER2 patients
Time Frame: The measure will be done when the genomic test is realised, that is about three weeks after patient's inclusion.
Percentage of HER2 classified patients using a genomic test among equivocal-HER2 patients
The measure will be done when the genomic test is realised, that is about three weeks after patient's inclusion.
The concordance between the second multidisciplinary decision-making meeting decision and the HER2 genomic test result
Time Frame: The measure will be done when the genomic test is realised, that is about three weeks after patient's inclusion.
Percentage of second multidisciplinary decision-making meeting decision in accordance with genomic test result and reasons justifying discrepancies (check-list and comments)
The measure will be done when the genomic test is realised, that is about three weeks after patient's inclusion.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
To compare results from different ISH methods used
Time Frame: The measure will be done when the genomic test is realised, that is about three weeks after patient's inclusion..
Comparison between all ISH (FISH, SISH, CISH, or DDISH) methods based upon the HER2-eligible classification (Wolff et al 2013)
The measure will be done when the genomic test is realised, that is about three weeks after patient's inclusion..
The concordance between local and centralized anatomopathologist HER2 status
Time Frame: The measure will be done when the genomic test is realised,that is about three weeks after patient's inclusion.
Concordance between local and centralized anatomopathologist HER2 status.
The measure will be done when the genomic test is realised,that is about three weeks after patient's inclusion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Jean Perrin

Collaborators

Roche Pharma AG
NanoString Technologies, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 16, 2017

Primary Completion (Actual)

May 28, 2019

Study Completion (Actual)

May 28, 2019

Study Registration Dates

First Submitted

June 19, 2017

First Submitted That Met QC Criteria

June 22, 2017

First Posted (Actual)

June 23, 2017

Study Record Updates

Last Update Posted (Actual)

July 25, 2019

Last Update Submitted That Met QC Criteria

July 24, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017-A00240-53

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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