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

Breast Cancer Clinical Trial

— EQUIVOK  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03197805
• Other study ID #: 2017-A00240-53
• Status: Terminated
• Phase: N/A
• Start date: October 16, 2017
• Est. completion date: May 28, 2019

Study information

• Verified date: July 2019
• Source: Centre Jean Perrin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: May 28, 2019
• Est. primary completion date: May 28, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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.

Locations

Country	Name	City	State
France	CHRU Jean Minoz	Besançon
France	Institut Bergonie	Bordeaux
France	Centre François Baclesse	Caen
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Georges François Leclerc	Dijon
France	CHU Albert Michalon	Grenoble
France	Hopital DUPUYTREN	Limoges
France	Centre Léon Bérard	Lyon
France	Institut Paoli Calmettes	Marseille
France	Institut de Cancérologie de Montpellier	Montpellier
France	Institut du Cancer COURLANCY	Reims
France	Institut Jean Godinot	Reims
France	Institut de Cancérologie de l'Ouest	Saint-Herblain
France	Centre Paul Strauss	Strasbourg
France	Institut Claudius Regaud	Toulouse
France	Institut de Cancérologie de Lorraine	Vandœuvre-lès-Nancy

Sponsors (3)

Lead Sponsor	Collaborator
Centre Jean Perrin	NanoString Technologies, Inc., Roche Pharma AG

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To compare results from different ISH methods used	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..
Other	The concordance between local and centralized anatomopathologist HER2 status	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.
Primary	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	The HER2 overexpression incidence according to RNA genomic profile among equivocal-HER2 patients	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.
Secondary	The concordance between the second multidisciplinary decision-making meeting decision and the HER2 genomic test result	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.