Chemotherapy-free Trastuzumab and Pertuzumab in HER2-positive Breast Cancer: FDG-PET Response-adapted Strategy. (PHERGain)
Breast Cancer

About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Written informed consent prior to beginning specific protocol procedures.
- 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) (breast cancer TNM classification)
- 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 standarized uptake value (SUVmax: maximum standarized uptake value) ≥1.5 x SUVmean (mean standarized uptake value) liver + 2 SD (standard deviation.
Multicentric/multifocal tumors will be allowed only if:
- Histological confirmation of at least two lesions.
- All tumors must be HER2-positive.
- 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.
Exclusion Criteria:
- Previous treatment with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy for invasive breast cancer.
- cT4 and/or cN3 tumors (TNM breast cancer classification)
- 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 abdomen and bone scan, except patients with subclinic M1 (metastases) 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.
- 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 arrythmias with the exception of benign premature ventricular contractions; conduction abnormality requiring a pacemaker; other arrhythmias not controlled with medication].
- 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 conditions 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.
LINGain sub-study: The LINGAIN project intends to include a total of 126 blood samples from PHERGain trial, as follows:
105 from patients treated with trastuzumab and pertuzumab ± endocrine therapy (according to HR status); 21 from patients treated with trastuzumab and pertuzumab + carboplatin and docetaxel.
Sites / Locations
- Institute Jules Bordet
- CLCC d'Auvergne. Centre Jean Perrin.
- Institute de Cancerologie de Laurraine
- Groupe Hospitalier Diaconesses
- Hopital Tenon
- Hospital Georges Pompidou
- Centre Paul Strauss
- Institut Claudius Régaud
- Kliniken Essen Mitte
- Klinikum der Med. Fakultät Halle
- National center for tumor disease NCT
- Städtisches Klinikum "St. Georg" Leipzig
- Hämatologisch-Onkologische Schwerpunktpraxis
- Clinical of Nuclear Medicine Technical University Munich
- Ospedale Maggiore Bologna
- Ospedale Antonio Perrino
- Istituto Ospedalieri di Cremona
- Ospedale Mantova
- Istituto Europeo di Oncologia
- Ospedale San Gerardo
- Ospedale Guglielmo de Saliceto
- Hospital Senhora da Oliveira
- Hospital Beatriz Angelo
- Hospital da Luz
- Hospital Fernando Fonseca
- Centro Hospitalar Sao Joao
- Hospital do Santo Antonio
- Centro Hospitalaer de Tras-os-Montes e Alto Douro
- ICO Badalona
- ICO l'Hospitalet
- Hospital Provincial de Castellón
- Hospital de Jaén
- Hospital Universitario Virgen de la Victoria
- Hospital San Joan de Reus
- Hospital Universitario A Coruña
- Hospital Vall D'Hebrón
- Hospital Clínic i Provincial de Barcelona
- Hospital Universitario de Burgos
- Hospital Reina Sofía
- ICO Girona
- Hospital Arnau de Vilanova
- Hospital La Paz
- Hospital Ramón y Cajal
- CHUS Santiago de Compostela
- Hospital Universitario Virgen del Rocío
- Hospital Arnau de Vilanova
- Hospital Clínic Universitari de Valencia
- Hospital Dr Peset
- Hospital General Universitari de Valencia
- Hospital Universitari i Politecnic La Fe
- Instituto Valenciano de Oncologia
- Hospital Lozano Blesa
- Hospital Universitario Miquel Servet
- Barts Cancer Institute
- The Christie NHS Foundation Trust
- Royal Cornwall Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Cohort A
Cohort B
Cohort C
Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel (during 4 cycles): PET responders or not responders after surgery: Continue with Perjeta+Herceptin+ Endocrine therapy (tamoxifen or letrozole) during 12 cycles A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study".
Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) during 2 cycles. PET responders: Perjeta+Herceptin+Endocrine therapy during 6 cycles. -Complete response: continue with Perjeta+Herceptin+ Endocrine therapy during 10 cycles -Non-complete response: Perjeta+Herceptin+ Carboplatin+ Docetaxel during 6 cycles and Perjeta+Herceptin+Endocrine therapy during 4 cycles. PET non-responders: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients with or without complete response will continue with Perjeta+Herceptin+Endocrine therapy during 10 cycles. A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study".
cohorts C if there is evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients will continue with Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) after surgery or no surgery.