Diagnostic HER2DX-guided Treatment for Patients wIth Early-stage HER2-positive Breast Cancer

NCT06446882 | Recruiting

• 1 other identifier: HCB-ONC002
• Study Type: interventional
• Target: 304
• Locations: 5 countries
• Sites: 29

Brief Summary

The primary goal of the DEFINITIVE trial is to demonstrate the effectiveness of the HER2DX diagnostic assay in enhancing the management of patients with early-stage HER2- positive breast cancer. Patients randomized to arm A will receive adjuvant treatment by physician´s choice, blinded to the diagnostic HER2DX test results. Patients randomized to Arm B will receive personalized treatment according to HER2DX results.

Conditions

HER2-positive Breast Cancer; Early-stage Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Global health status (GHS) scale from the EORTC QLQ-C30 questionnaire

  The GHS scale is based on two 7-point questions (from very poor to excellent, items 29-30 from EORTC QLQ-C30 questionnaire). Following EORTC scoring manuals, a linear transformation will be used to standardize the GHS scale to a 0-100 scale.

  Up to 5 years

• Score from the FACIT Fatigue Scale

  The FACIT Fatigue Scale, version 4 will be used to evaluate PRO measures of quality-of-life concerns related to fatigue. The FACIT Fatigue Scale is a 13-item questionnaire designed to measure fatigue and its impact on daily life in individuals with various health conditions. Respondents rate their fatigue experiences over the past week on a scale from 0 to 4, with higher scores indicating less fatigue. The total score ranges from 0 to 52.

  Up to 5 years

Secondary Outcomes (12)

• Functional and symptom scales from the EORTC QLQ-C30 questionnaire.

  Up to 5 years

• Score of the EuroQol-5D

  Up to 5 years

• pCR rates

  Up to 5 years

• Residual cancer burden (RCB)

  Up to 5 years

• Invasive disease-free survival (iDFS)

  Up to 5 years

Study Arms (2)

Arm A: Treatment by physician´s choice without the diagnostic test results

OTHER

Treatment by physician´s choice, blinded to the diagnostic HER2DX test results

Other: Treatment by physician´s choice, blinded to the diagnostic HER2DX test results

Arm B: Personalized treatment according to molecular diagnosis with HER2DX

EXPERIMENTAL

Personalized treatment according to molecular diagnosis with non-blinded HER2DX results

Device: Personalized treatment according to molecular diagnosis with HER2DX

Interventions

Personalized treatment according to molecular diagnosis with HER2DX DEVICE

Patients with HER2DX high-risk disease: * Neoadjuvant treatment: * High HER2DX pCR score: paclitaxel per 12 weeks + trastuzumab +/- pertuzumab per 4-5 cycles. * Medium HER2DX pCR score: carboplatin + paclitaxel per 12-18 (or docetaxel per 4-6 cycles) + trastuzumab +/- pertuzumab per 4-7 cycles. * Low HER2DX pCR score: standard of care neoadjuvant CT regimens and HER2 blockade at the investigator's choice. * Adjuvant treatment: * pCR at surgery; Trastuzumab +/- pertuzumab up to a total of 18 cycles (including neoadjuvant and adjuvant therapy). * No pCR at surgery: T-DM1 per 14 cycles. Patients with HER2DX low-risk disease: * Neoadjuvant treatment: paclitaxel per 12 weeks + trastuzumab +/- pertuzumab per 4-5 cycles. * Adjuvant treatment will be according to the pCR status at surgery: * pCR at surgery: trastuzumab or no adjuvant treatment. * No pCR at surgery: trastuzumab or T-DM1.

Arm B: Personalized treatment according to molecular diagnosis with HER2DX

Treatment by physician´s choice, blinded to the diagnostic HER2DX test results OTHER

Patients randomized in ARM A will be treated with standard of care neoadjuvant CT regimens and HER2 blockade at the investigator's choice validated by national and/or international guidelines.

Arm A: Treatment by physician´s choice without the diagnostic test results

Eligibility Criteria

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

You may qualify if:

• Signed informed consent must be obtained prior to any trial-specific procedure. Note: Candidate patients in France must be affiliated to a Social Security System (or equivalent).
• Male/female patients who are at least 18 years of age on the day of signing informed consent.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Eligible for any of the following drugs: taxane, carboplatin, trastuzumab, pertuzumab and T-DM1 therapy.
• Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast untreated and recently diagnosed.
• Stage at presentation: cT1 cN1-2 or cT2-3 cN0-2 as determined by AJCC staging system, 8th edition (specifically in accordance with Anatomic Stage group rules).
• Note: Axillary lymph node status must be assessed by fine needle biopsy or core biopsy. This procedure at screening will be omitted if there is no suspicion for positive axillary lymph node(s) radiographically or if a pathological report of suspicious lymph nodes of the results of a fine needle biopsy or core biopsy is available prior to the screening period.
• Absence of distant metastasis (i.e., cM0).
• Patients with multifocal tumors (more than one mass confined to the same quadrant as primary tumor) are eligible provided at least one focus is sampled and locally confirmed as HER2-positive.
• Patients with multicentric tumors (multiple tumors involving more than one quadrant) are eligible provided all discrete lesions are sampled and locally confirmed as HER2-positive.
• Note: In patients with multifocal or multicentric breast cancer, the largest lesion should be measured to determine T stage and to performe the HER2DX test.
• HER2 positivity defined as either of the following: IHC 3+ or HER2 2+/ ISH positive as per most recent ASCO- CAP guideline according to the local laboratory as determined on the most recently analyzed tissue sample.
• ER/PR status determined local based on pretreatment breast biopsy material according to the most recent ASCO/CAP guidelines.
• Candidates for neoadjuvant treatment.
• Patient agreement to undergo appropriate surgical management, including axillary lymph node surgery and partial or total mastectomy, after completion of neoadjuvant treatment

You may not qualify if:

• Stage IV (metastatic) breast cancer.
• Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, carboplatin, T-DM1, docetaxel or paclitaxel.
• Patients with synchronous bilateral invasive breast cancer.
• Prior systemic therapy for treatment of breast cancer.
• Ulcerating or inflammatory breast cancer.
• Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes.
• Sentinel lymph node procedure or axillary lymph node dissection prior to initiation of neoadjuvant therapy.
• Patients with a history of previous breast cancer are excluded. Patients with a history of any other cancers (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years are excluded. For patients with a history of other non-breast cancerscancerscancers within 3 years and considered of low risk of recurrence per investigator's judgment (for example, papillary thyroid cancer treated with surgery), eligibility is to be discussed with the Sponsor.
• Cardiopulmonary dysfunction as defined by any of the following prior to randomization:
• History of congestive heart failure of any classification.
• Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease.
• High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate \> 100/min at rest, significant ventricular arrhythmia \[ventricular tachycardia\], or higher-grade atrioventricular \[AV\]-block \[second degree AV-block Type 2 \[Mobitz 2\] or third-degree AV-block\]).
• Significant symptoms (Grade \> 1) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia.
• Myocardial infarction within 12 months prior to randomization.
• Evidence of transmural infarction on ECG.

Sponsors & Collaborators

• Austrian Breast & Colorectal Cancer Study Group: collaborator
• UNICANCER: collaborator
• Westdeutsche Studiengruppe GmbH (WSG): collaborator
• Istituto Oncologico Veneto IRCCS: collaborator
• University College Cork: collaborator
• University of Padova: collaborator
• Istituto Europeo di Oncologia: collaborator
• National University of Ireland, Galway, Ireland: collaborator
• The Sheba Fund for Health Services and Research: collaborator
• Erasmus University Rotterdam: collaborator
• Medical University of Vienna: collaborator
• Institut Català d'Oncologia: collaborator
• Europa Donna: collaborator
• Reveal Genomics: collaborator
• Fundacio Clinic Barcelona: lead
• SOLTI Breast Cancer Research Group: collaborator

Study Sites (29)

MUG-Univ.-Klinik für Frauenheilkunde und Geburtshilfe, Klinische Abteilung für Gynäkologie

Graz, Austria

RECRUITING

Lkh Hochsteiermark-Leoben

Leoben, Austria

RECRUITING

Ordensklinikum Linz, Barmherzige Schwestern, Bhs

Linz, Austria

RECRUITING

Uniklinikum Salzburg

Salzburg, Austria

RECRUITING

Universitätsklinikum St.Pölten

Sankt Pölten, Austria

RECRUITING

Hanusch Krankenhaus

Vienna, Austria

RECRUITING

Klinik Hietzing, Gynäkologische Abteilung - Karl Landsteiner Institut für gyn. Onkologie

Vienna, Austria

RECRUITING

Medizinische Universität Wien, Allg. Gynäkologie und Gyn. Onkologie

Vienna, Austria

RECRUITING

Klinikum Wels-Grieskirchner

Wels, Austria

RECRUITING

Sainte-Catherine - Institut du Cancer Avignon-Provence

Avignon, France

RECRUITING

Polyclinique Bordeaux Nord

Bordeaux, France

RECRUITING

Centre León Bérard

Léon, France

RECRUITING

Institut Paoli Calmettes

Marseille, France

RECRUITING

Institut de Cancérologie de Lorraine

Nancy, France

RECRUITING

Gustave Roussy

Paris, France

RECRUITING

Oncopole Claudius Regaud, IUCT-Oncopole

Toulouse, France

RECRUITING

Sheba Medical Center

Ramat Gan, Israel

RECRUITING

Istituto Europeo di Oncologia

Milan, Italy

RECRUITING

Institute Oncology Veneto

Padua, Italy

RECRUITING

Instituto Catalán de Oncología (ICO) - Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

Hospital Universitario Clínico San Cecilio

Granada, Granada, 18007, Spain

RECRUITING

Hospital Clínico Universitario de Santiago

Santiago de Compostela, La Coruña, 15706, Spain

RECRUITING

Complejo Asistencial Universitario de León

León, León, 24008, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

RECRUITING

Hospital Clínico Universitario Virgen de Arrixaca

Murcia, Murcia, 30120, Spain

RECRUITING

Hospital Universitario Sant Joan de Reus

Reus, Tarragona, 42301, Spain

RECRUITING

Hospital Universitario de Basurto

Bilbao, Vizcaya, 48013, Spain

RECRUITING

Instituto Catalán de Oncología (ICO) - Badalona

Badalona, Spain

RECRUITING

Hospital Universitario de Salamanca

Salamanca, Spain

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Tomás Pascual, MD

CONTACT

932 27 57 07; definitive@gruposolti.org

Olga Martínez, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2024
• First Posted: June 6, 2024
• Study Start: October 11, 2024
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: February 20, 2026

Record last verified: 2026-02

Locations

IL (1); AU (9); FR (7); IT (2); ES (10)