Diagnostic HER2DX-guided Treatment for Patients wIth Early-stage HER2-positive Breast Cancer
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorFundacio Clinic Barcelona
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Personalized treatment according to molecular diagnosis with HER2DX
DevicePatients 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.
Treatment by physician´s choice, blinded to the diagnostic HER2DX test results
Other interventionPatients 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.
Treatment groups
304 Participants
are divided into 2 treatment groupsGroup A: Arm A: Treatment by physician´s choice without the diagnostic test resultsOther 1 intervention
Group B: Arm B: Personalized treatment according to molecular diagnosis with HER2DXExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Up to 5 years2
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.
Time frame
Up to 5 yearsSecondary outcomes
1
Functional and symptom scales from the EORTC QLQ-C30 questionnaire.
Change from baseline in all other functional and symptom scales (items 1 to 28) from the EORTC QLQ-C30 questionnaire version 3.0 to assesses cancer-related symptoms, impacts, and treatment-related symptoms. The items are rated on a 4-point rating scale ranging from 0 ("not at all") to 4 ("very much").
Time frame
Up to 5 years2
Score of the EuroQol-5D
Change from baseline in the score of the EuroQol-5D. The 5-level version EQ-5D-5L is a 6-item generic patient-reported preference-based instrument designed to assess health status of patients. The EQ-5D-5L consists of 2 sections: * the EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels of severity: the dimensions of mobility, self-care, and usual activity are rated ranging from 1 (no problem completing task) to 5 (unable to complete task) while the dimensions of pain/discomfort and anxiety/depression are rated ranging 1 (no symptom) to 5 (extreme symptom). * the EuroQoL visual analogue scale (EQ-VAS) is for patients to self-rate their (global) health state utilizing a vertically oriented visual analogue scale where 100 represents the "best possible health state" and 0 represents the "worst possible health state".
Time frame
Up to 5 years3
pCR rates
pCR rates between groups at randomization and according to the predefined HER2DX pCR score as a continuous variable and as group categories. pCR will be defined as the complete absence of invasive carcinoma in the breast and axillary lymph nodes on histological examination at the time of definitive surgery, irrespective of in situ carcinoma in the breast.
Time frame
Up to 5 years4
Residual cancer burden (RCB)
RCB between groups at randomization and according to HER2DX pCR score as a continuous variable and as group categories. Residual cancer burden (RCB) is defined as classes 0, 1, 2 and 3, according to the MD Anderson Cancer Center recommendations by local evaluation.
Time frame
Up to 5 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Fundacio Clinic Barcelona
Lead sponsor
SOLTI Breast Cancer Research Group
Collaborator
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
Source ClinicalTrials.gov