Chemotherapy-Free pCR-Guided Strategy With Trastuzumab-pertuzumab and T-DM1 in HER2-positive Early Breast Cancer

NCT04733118 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: MedOPP293
• Study Type: interventional
• Target: 393
• Locations: 5 countries
• Sites: 41

Brief Summary

This is a multicenter, open-label, single-arm, one-stage, phase II study to assess the efficacy of a chemotherapy-free pathological complete response (pCR)-guided strategy with trastuzumab and pertuzumab (given as a subcutaneous fixed-dose combination) and T-DM1, for patients with previously untreated HER2-positive early breast cancer.

Conditions

Early Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 3-year recurrence-free interval (3y-RFI)

  3-year recurrence-free interval (3y-RFI) defined as time from start of treatment in adjuvant setting until recurrence, new invasive disease, or death from breast cancer. Recurrence will be defined in accordance with the standardized efficacy endpoints (STEEP) criteria.

  3 years

• Global health status decline

  Global health status decline rate at 1 year from start of neoadjuvant treatment, defined as the rate of patients with a ≥10% global health status decline at 1 year from start of neoadjuvant treatment as assessed by the Global Health Status/QoL EORTC-QLC-C30 scale and its breast cancer module QLQ-BR23.

  1 year

Secondary Outcomes (22)

• pathological complete response (pCR)

  after neoadjuvant treatment (8 cycles, an average of 6months)

• pathological complete response (pCR) according to hormone receptor (HR) status

  after neoadjuvant treatment (8 cycles, an average of 6months)

• Residual cancer burden (RCB)

  after neoadjuvant treatment (8 cycles, an average of 6months)

• Breast-conserving surgery (BCS)

  after neoadjuvant treatment (8 cycles, an average of 6months)

• Response rate BCS

  after neoadjuvant treatment (8 cycles, an average of 6months)

Study Arms (1)

Patient HER 2+ IHC 3+

EXPERIMENTAL

Patients ≥18 years of age with previously untreated HER2-positive (HER2\[+\]) (Immunohistochemistry \[IHC\] 3+) invasive carcinoma according to the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria and tumor size between \>5 to 25 mm by breast magnetic resonance imaging (MRI) and node-negative status by clinical exam, MRI, and ultrasound. Patients must have not been previously treated with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy (ET) for invasive breast cancer. Patients with metastatic disease are not eligible. In patients with suspected axillary node involvement, a negative fine needle aspiration biopsy (FNAB) will be mandatory

Drug: Trastuzumab and Pertuzumab (FDC SC) and T-DM1

Interventions

Trastuzumab and Pertuzumab (FDC SC) and T-DM1 DRUG

Patients will receive Trastuzumab and Pertuzumab as a subcutaneous fixed-dose combination (PH FDC SC) (± ET depending on HR status) for 8 3-week cycles, on day 1 only. ET will consist of letrozole for post-menopausal women or tamoxifen ± ovarian function suppression (OFS) for pre-menopausal women administered continuously. Men will receive tamoxifen. After completing neoadjuvant therapy, a final breast MRI will be performed 2 weeks prior to surgery. Surgery will be performed within 4 weeks after completion of the last cycle of PH FDC SC. Adjuvant systemic therapy will start within 4 weeks from surgery. There will be three different cohorts depending on pathological report: * Cohort A: PH FDC SC ± ET for 10 additional 3-week cycles * Cohort B: T-DM1 ± ET for 10 cycles * Cohort C: T-DM1 ± ET for 10 cycles, with possibility of physician's choice chemotherapy before adjuvant T-DM1.

Also known as: Trastuzumab emtansine, Phesgo, Kadcyla

Patient HER 2+ IHC 3+

Eligibility Criteria

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

You may qualify if:

• Patients will be included in the study only if they meet ALL of the following 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 or 1.
• Histologically proven invasive carcinoma of the breast.
• Tumor size must be between ≥ 5mm and ≤30mm in greatest dimension using breast MRI. Note: Although tumors between ≥ 5mm and ≤ 10mm are not considered target lesions by RECIST v1.1, we will consider these lesions as targets to follow-up.
• Patients must have node-negative breast cancer by clinical exam, MRI and ultrasound according to the American Joint Committee on Cancer (AJCC) 8th edition.
• Centrally confirmed HER2\[+\] status with IHC score 3+.
• Known estrogen receptor (ER) and progesterone receptor (PgR) status prior to study entry that should be performed by immunohistochemical methods according to the local institution standard protocol.
• Normal left ventricular function and diastolic function (left ventricular ejection fraction \[LVEF\] ≥55%) as assessed by echocardiogram or multiple-gated acquisition scan (MUGA) documented within ≤28 days prior to first dose of study treatment.
• Adequate bone marrow, liver, and renal function:
• Hematological: White blood cell (WBC) count \> 3.0 × 109/L, absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100.0 × 109/L, and hemoglobin ≥ 10.0 g/dL (≥ 6.2 mmol/L).
• 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 × ULN or creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.

You may not qualify if:

• Any patient meeting ANY of the following criteria will be excluded from the study:
• Any previous treatment, including chemotherapy, anti-HER2 therapy, radiation therapy, or ET for invasive breast cancer (except for breast carcinoma in situ of the contralateral breast cancer, in the last five years before treatment initiation in this study).
• HER2 disease with IHC score 0, 1+ or 2+ and in situ hybridization (ISH) positive result.
• Evidence of metastatic disease. Note: All patients must be willing to undergo chest and pelvis computed tomography (CT)/MRI scan before enrolment to prove no evidence of metastatic disease. Bone scan will be performed at baseline only if there is suspicion of bone metastases. If a bone scan cannot be performed, an alternative is PET/CT using 18F-labeled sodium fluoride (18F-fluoride PET/CT).
• Patients with bilateral breast cancer.
• 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.
• Uncontrolled hypertension (systolic \> 150 mm Hg and/or diastolic \> 100 mm Hg) despite adequate antihypertensive treatment.
• Serious cardiac illness or medical conditions including, but not confined to, the following:
• History of NCI CTCAE v5.0 Grade ≥ 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class ≥ II.
• 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, such as second-degree AV-block Type 2 \[Mobitz II\] or third-degree AV-block).
• Serious cardiac arrhythmia or severe conduction abnormality not controlled by adequate medication.
• Angina pectoris requiring anti-angina medication.
• Clinically significant valvular heart disease.
• Evidence of transmural infarction on electrocardiogram (ECG).

Sponsors & Collaborators

• MedSIR: lead
• Hoffmann-La Roche: collaborator

Study Sites (41)

UMHAT Sveti Ivan Rilski EAD Department of Medical Oncology

Sofia, Bulgaria

Location

Praxisnetzwerk Hämatologie und intern. Onkologie

Cologne, Germany

Location

Evangelisches Krankenhaus Bethesda

Duisburg, Germany

Location

Kliniken Essen Mitte

Essen, Germany

Location

Universitätsklinikum Essen Frauenklinik

Essen, Germany

Location

Universitätsklinikum Mannheim GmbH

Manheim, Germany

Location

Klinikum Ernst von Bergmann

Potsdam, Germany

Location

Békés county hospital

Békés, Hungary

Location

Tolna County Balassa János Hospital

Szekszárd, Hungary

Location

Azienda Ospedaliero Universitaria Di Bologna - Policlinico S.Orsola-Malpighi

Bologna, Italy

Location

AO Ospedale Civile Legnano

Milan, Italy

Location

Istituto Europeo di Oncologia - NC

Milan, Italy

Location

Ospedale San Gerardo

Monza, Italy

Location

Azienda Ospedaliero-Universitaria di Parma

Parma, Italy

Location

Ospedale Guglielmo da Saliceto

Piacenza, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Italy

Location

ICO L'Hospitalet - Instituto Catalán de Oncología

L'Hospitalet de Llobregat, Barcelona, 08007, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Cordoba, 14004, Spain

Location

Hospital Universitari San Joan de Reus

Reus, Tarragona, Spain

Location

Centro Oncológico de Galicia

A Coruña, 15009, Spain

Location

Hospital Universitario A Coruña

A Coruña, Spain

Location

Hospital General Universitario de Alicante

Alicante, Spain

Location

Institut Català d' Oncologia Badalona (ICO)

Badalona, Spain

Location

Hospital Universitari Dexeus - Grupo Quirónsalud

Barcelona, Spain

Location

VHIO Vall d'Hebron Institute of Oncology

Barcelona, Spain

Location

Hospital Universitario de Basurto

Bilbao, 48013, Spain

Location

Consorcio Hospitalario Provincial De Castelló

Castellon, 12002, Spain

Location

Hospital Universitario Clínico San Cecilio de Granada

Granada, Spain

Location

Complejo Hospitalario de Jaen

Jaén, Spain

Location

Complejo Asistencial Universitario de León

León, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Quirón San Camilo- Ruber Juan Bravo

Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Hospital Universitario de Torrejón

Torrejón, Spain

Location

Instituto Valenciano de Oncología (IVO)

Valencia, 46009, Spain

Location

Hospital La Fe

Valencia, 46026, Spain

Location

Consorcio Hospital General de Valencia

Valencia, Spain

Location

Hospital Arnau de Vilanova de Valencia

Valencia, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; pertuzumab; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Antonio Llombart-Cussac, MD

  Arnau de Vilanova Hospital, Valencia (Spain)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2020
• First Posted: February 1, 2021
• Study Start: August 5, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (6); ES (25); BU (1); HU (2); IT (7)