Chemotherapy-free trastuzumab and pertuzumab in HER2-positive breast cancer after FDG-PET response-adapted strategy. The PHERGain study
- Conditions
- HER2- positive breast cancer
- Registration Number
- 2023-509923-42-00
- Lead Sponsor
- Medica Scientia Innovation Research S.L.
- Brief Summary
• 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruitment ended
- Sex
- Not specified
- Target Recruitment
- 345
Written informed consent prior to beginning specific protocol procedures.
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.
Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
Patient must be accessible for treatment and follow-up.
Female or male patients ≥ 18 years of age.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
Histologically proven invasive breast cancer.
Operable breast cancer (cT1-3 and/or cN0-2 tumors).
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.
Centrally confirmed HER2-positive disease according to the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria.
Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status locally determined prior to study entry.
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).
Previous treatment with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy for invasive breast cancer.
Active uncontrolled infection at the time of enrollment.
Current known infection with HIV, hepatitis B virus, or hepatitis C virus.
Patients with pulmonary disease requiring continuous oxygen therapy.
Previous history of bleeding diathesis.
Patient is currently receiving anti-coagulant therapy, chronic treatment with corticosteroids, or another immunosuppressive agent (standard premedication for chemotherapy and local applications are allowed).
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.
Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator´s judgment, contraindicate her participation in the clinical study.
Concurrent participation in other clinical trial, except other translational studies.
History of receiving any investigational treatment within 28 days prior to randomization.
Pregnant or breast-feeding women or patients not willing to apply highly effective contraception as defined in the protocol.
cT4 and/or cN3 tumors.
Bilateral breast cancer.
Evidence of metastatic disease by routine clinical assessment [chest x-ray, liver ultrasound, and bone scan; or computed tomography (CT) scan of thorax and and abdomen and bone scan], except patients with subclinical M1 at baseline only according to 18Ffluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) that will be allowed to be included into Cohort C.
Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances.
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.
Left ventricular ejection fraction (LVEF) below 55% as determined by multiple-gated acquisition (MUGA) scan or echocardiography (ECHO).
Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) despite adequate antihypertensive treatment.
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].
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 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 recurrence, new invasive disease, or death by any cause. Recurrence will be defined in accordance with the standardized efficacy endpoints (STEEP) criteria. The primary analysis will be to estimate 3-year iDFS rate in cohort B. 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 recurrence, new invasive disease, or death by any cause. Recurrence will be defined in accordance with the standardized efficacy endpoints (STEEP) criteria. The primary analysis will be to estimate 3-year iDFS rate in cohort B.
- Secondary Outcome Measures
Name Time Method 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 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). 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). 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). 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). 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). 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). 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). 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). 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). 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, 5, and 7-year iDFS (cohort A; cohort B [with the exception of 3-year iDFS]; cohorts A/B by PET responder status, HR status, and HER2 status). 3, 5, and 7-year iDFS (cohort A; cohort B [with the exception of 3-year iDFS]; cohorts A/B by PET responder status, HR status, and HER2 status).
3, 5, and 7-year DDFS (cohort A; cohort B; cohorts A/B by PET responder status, HR status, and HER2 status). 3, 5, and 7-year DDFS (cohort A; cohort B; cohorts A/B by PET responder status, HR status, and HER2 status).
3, 5, and 7-year DFS (cohort A; cohort B; cohorts A/B by PET responder status, HR status, and HER2 status). 3, 5, and 7-year DFS (cohort A; cohort B; cohorts A/B by PET responder status, HR status, and HER2 status).
3, 5, and 7-year adapted iDFS, DDFS, and DFS (patients with subclinical M1 at baseline by 18F-FDG PET/CT – cohort C). 3, 5, and 7-year adapted iDFS, DDFS, and DFS (patients with subclinical M1 at baseline by 18F-FDG PET/CT – cohort C).
3, 5, and 7-year EFS (cohort A; cohort B). 3, 5, and 7-year EFS (cohort A; cohort B).
3, 5, and 7-year OS (cohort A; cohort B; cohort C; cohorts A/B by PET responder status, HR status, and HER2 status). 3, 5, and 7-year OS (cohort A; cohort B; cohort C; cohorts A/B by PET responder status, HR status, and HER2 status).
PFS (patients with subclinical M1 at baseline by 18F-FDG PET/CT – cohort C). PFS (patients with subclinical M1 at baseline by 18F-FDG PET/CT – cohort C).
Adverse events, grade 3-4 adverse events, related adverse events, serious adverse events, related serious adverse events, and adverse events leading to discontinuation (cohort A; cohort B; cohort C; cohorts A/B by PET responder status, HR status, and HER2 status). Adverse events, grade 3-4 adverse events, related adverse events, serious adverse events, related serious adverse events, and adverse events leading to discontinuation (cohort A; cohort B; cohort C; cohorts A/B by PET responder status, HR status, and HER2 status).
Trial Locations
- Locations (40)
Klinikum rechts der Isar der TU Muenchen AöR
🇩🇪Munich, Germany
KEM I Evang. Kliniken Essen-Mitte gGmbH
🇩🇪Essen, Germany
Universitaetsklinikum Halle (Saale) AöR
🇩🇪Halle Saale, Germany
Hospital Da Luz S.A.
🇵🇹Lisbon, Portugal
Hospital Professor Doutor Fernando Fonseca E.P.E.
🇵🇹Amadora, Portugal
Hospital Beatriz Angelo
🇵🇹Loures, Portugal
Unidade Local De Saude Do Alto Ave E.P.E.
🇵🇹Guimaraes, Portugal
Sao Joao University Hospital Center
🇵🇹Porto, Portugal
Fundacion Instituto Valenciano De Oncologia
🇪🇸Valencia, Spain
Hospital Universitario Y Politecnico La Fe
🇪🇸Valencia, Spain
Scroll for more (30 remaining)Klinikum rechts der Isar der TU Muenchen AöR🇩🇪Munich, GermanyFranziska KotzurSite contact004908941402446franziska.kotzur@mri.tum.de