HER2-positive breast cancer MedDRA version: 23.0 Level: PT Classification code 10065430 Term: HER2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Medica Scientia Innovation Research (MedSIR)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Written informed consent prior to beginning specific protocol procedures. 2) Female or male patients = 18 years of age. 3) Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 4) Histologically proven invasive breast cancer. 5) Operable breast cancer (cT1-3 and/or cN0-2 tumors). 6) Tumor size larger than or equal to 1.5 centimeter (cm) in diameter by magnetic resonance imaging (MRI) or ultrasound with a significant 18F-FDG uptake defined as maximum standardized uptake value (SUVmax) =1.5 x SUVmean liver + 2 SD. Multicentric/multifocal tumors will be allowed only if: 1. Histological confirmation of at least two lesions. 2. All tumors must be HER2-positive. 3. Largest lesion must be larger than or equal to 1.5 cm in diameter by MRI or ultrasound. 7) Centrally confirmed HER2-positive disease according to the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria. 8) Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status locally determined prior to study entry. Patient has adequate bone marrow, liver, and renal function: 9) Hematological: White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophil count (ANC) = 1.5 x 109/L, platelet count = 100.0 x109/L, and hemoglobin = 10.0 g/dL (= 6.2 mmol/L). 10) Hepatic: total bilirubin = institutional upper limit of normal (ULN) (except for Gilbert’s syndrome); alkaline phosphatase (ALP) = 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) = 1.5 times ULN. 11) Renal: serum creatinine = 1.5 x ULN or creatinine clearance = 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. 12) Patient must be accessible for treatment and follow-up. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Previous treatment with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy for invasive breast cancer. 2) cT4 and/or cN3 tumors. 3) Bilateral breast cancer. 4) Evidence of metastatic disease by routine clinical assessment ?chest x-ray, liver ultrasound, and bone scan; or computed tomography (CT) scan of thorax and abdomen and bone scan?, except patients with subclinic M1 at baseline only according to 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) that will be allowed to be included into Cohort C. 5) Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances. 6) History of other malignancy within the last five years prior to first dose of study drug administration, except for curatively treated basal and squamous cell carcinoma of the skin and/or in situ cervical carcinoma. 7) Left ventricular ejection fraction (LVEF) below 55% as determined by multiple-gated acquisition (MUGA) scan or echocardiography (ECHO). 8) Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) despite adequate antihypertensive treatment. 9) Clinically significant cardiovascular disease [stroke, unstable angina pectoris, or documented myocardial infarction within six months prior to study entry; history of documented congestive heart failure (CHF) (New York Heart Association II-III-IV); symptomatic pericarditis; documented cardiomyopathy; ventricular arrytmhias with the exception of benign premature ventricular contractions; conduction abnormality requiring a pacemaker; other arrhythmias not controlled with medication]. 10) Active uncontrolled infection at the time of enrollment. 11) Current known infection with HIV, hepatitis B virus, or hepatitis C virus. 12) Patients with pulmonary disease requiring continuous oxygen therapy. 13) Previous history of bleeding diathesis. 14) Patient is currently receiving anti-coagulant therapy, chronic treatment with corticosteroids, or another immunosuppressive agent (standard premedication for chemotherapy and local applications are allowed). 15) Major surgical procedure or significant traumatic injury within 14 days prior to randomization or anticipation of need for major surgery within the course of the study treatment. 16) Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator´s judgment, contraindicate her participation in the clinical study. 17) Concurrent participation in other clinical trial, except other translational studies. 18) History of receiving any investigational treatment within 28 days prior to randomization. 19) Pregnant or breast-feeding women or patients not willing to apply highly effective contraception as defined in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To assess the early metabolic effects of neoadjuvant treatment with trastuzumab and pertuzumab (± endocrine therapy) on the primary tumor and axillary lymph nodes and their predictive value for pathologic complete response (pCR) in the breast and axilla. •To assess 3-year invasive disease-free survival (iDFS) in patients with HER2-positive breast cancer treated with neoadjuvant trastuzumab and pertuzumab (± endocrine therapy) using a FDG-PET response-adapted strategy.;Secondary Objective: To assess efficacy by other pCR definitions [pCR in the breast only and Residual Cancer Burden (RCB) score]. • To compare the rate of pCR between the treatment groups by 18F-FDG PET/CT response, hormone receptor (HR) status, HER2 status, and tumor stage. • To compare the rate of conversion to breast conserving surgery between the treatment groups. • To compare the overall response rate (ORR) by 18F-FDG PET/CT between the treatment groups. • To analyze optimal 18F-FDG PET/CT cut-off for pCR. • To analyze other 18F-FDG PET quantification parameters beside SUVmax for pCR. • To compare the ORR by MRI between the treatment groups. • To evaluate changes in health-related quality of life assessments from baseline using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. • To assess 3-year iDFS between the treatment groups by 18F-FDG PET/CT response, HR status, and HER2 status. ;Primary end point(s): •The first co-primary endpoint is to evaluate the rate of pCR as defined by the absence of invasive disease in the breast and axilla (ypT0/isN0) at the time of surgery achieved with the combination of trastuzumab and pertuzumab (± endocrine therapy) as exclusive neoadjuvant treatment in PET responders patients (cohort B/PET responders) [PET/CT positive predictive value (PPV) for a pCR among patients who are PET responders]. •The second co-primary endpoint is to evaluate 3-year iDFS rate defined as time from the first date of no disease (i.e., date of surgery) to invasive recurrenc | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): pCR rates in the breast and axilla (ypT0/isN0) (cohort A; cohort B; cohorts A/B by PET responder status). • pCR rates in the breast (ypT0/is) (cohort A; cohort B; cohorts A/B by PET responder status). • RCB score (cohort A; cohort B; cohorts A/B by PET responder status). • pCR rates in the breast and axilla (ypT0/isN0) (cohort A; cohort B; cohorts A/B by PET responder status; HR status, HER2 status and tumor stage). • Rate of breast conserving surgery (cohort A; cohort B; cohorts A/B by PET responder status). • 18F-FDG PET/CT response rate (according to the adapted EORTC criteria) (cohort A; cohort B). • Optimal 18F-FDG PET/CT cut-off for pCR (cohort A; cohort B). • Other 18F-FDG PET quantification parameters beside SUVmax for pCR (cohort A; cohort B). • MRI response rate (according to the RECIST criteria version 1.1) (cohort A; cohort B; cohorts A/B by PET responder status). • Health-related quality of life (EORTC QLQ-C30 and QLQBR23 questionnaires) (cohort A; cohort B; cohort C; cohorts A/B by PET responder status). • 3-year iDFS (cohort A; cohort B; cohort C; cohorts A/B by PET responder status, HR status, and HER2 status). • 3-year DDFS (cohort A; cohort B; cohort C; cohorts A/B by PET responder status, HR status, and HER2 status). • 3-year DFS (cohort A; cohort B; cohort C; cohorts A/B by PET responder status, HR status, and HER2 status). • OS (cohort A; cohort B; cohort C; cohorts A/B by PET responder status, HR status, and HER2 status).;Timepoint(s) of evaluation of this end point: 3 years from surgery | — |
Countries
Belgium, France, Germany, Italy, Portugal, Spain, United Kingdom
Contacts
Public ContactCrina Popa
Medica Scientia Innovation Research (MedSIR)
Outcome results
None listed