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

NCT03197805 | Terminated

• 1 other identifier: 2017-A00240-53
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 16

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.

Conditions

Breast Cancer

Keywords

Equivocal Her 2; Genomic test

Outcome Measures

Primary Outcomes (1)

• The modification of therapeutical decision between the first and the second multidisciplinary decision-making meeting (MD-MM) using a genomic testing

  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 Outcomes (2)

• The HER2 overexpression incidence according to RNA genomic profile 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

  The measure will be done when the genomic test is realised, that is about three weeks after patient's inclusion.

Other Outcomes (2)

• To compare results from different ISH methods used

  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

  The measure will be done when the genomic test is realised,that is about three weeks after patient's inclusion.

Study Arms (1)

Use of PAM 50 test in Her2 equivocal breast cancer patient

EXPERIMENTAL

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

Interventions

PAM 50 test DIAGNOSTIC_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.

Use of PAM 50 test in Her2 equivocal breast cancer patient

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Jean Perrin: lead
• Roche Pharma AG: collaborator
• NanoString Technologies, Inc.: collaborator

Study Sites (16)

CHRU Jean Minoz

Besançon, 25030, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre François Baclesse

Caen, 14000, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63000, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

CHU Albert Michalon

Grenoble, 38043, France

Location

Hopital DUPUYTREN

Limoges, 87042, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Institut de Cancérologie de Montpellier

Montpellier, 34298, France

Location

Institut Jean Godinot

Reims, 51056, France

Location

Institut du Cancer COURLANCY

Reims, 51100, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, 44805, France

Location

Centre Paul Strauss

Strasbourg, 67065, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Marie-Ange MOURET-REYNIER, MD

  Centre Jean Perrin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cohort longitudinal follow up

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: June 23, 2017
• Study Start: October 16, 2017
• Primary Completion: May 28, 2019
• Study Completion: May 28, 2019
• Last Updated: July 25, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (16)