Elderly Metastatic Breast Cancer: Pertuzumab-Herceptin vs Pertuzumab-Herceptin-Metronomic Chemotherapy, Followed by T-DM1

Pertuzumab + Trastuzumab (PH) Versus PH Plus Metronomic Chemotherapy (PHM) in the Elderly HER2+ Metastatic Breast Cancer Population Who May Continue on T-DM1 Alone Following Disease Progression While on PH / PHM: an Open-label Multicentre Randomized Phase II Selection Trial of the EORTC Elderly Task Force and Breast Cancer Group

Chemotherapy and HER2 targeted agents can improve survival significantly in metastatic breast cancer. Chemotherapy however is associated with significant side-effects and can impact on Quality of Life and functionality in older patients.

The investigators aim to establish HER2 targeted regimens with minimal toxicity in order to delay or even avoid the use of classical chemotherapy because of competing risks of death in this frail/elderly patient group.

Study Overview

• Status: Completed
• Conditions: Elderly Metastatic Breast Cancer Population
• Intervention / Treatment: Drug: Pertuzumab + trastuzumab; Drug: Pertuzumab + trastuzumab + metronomic chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium
    • UZ Antwerpen
  • Brussels, Belgium
    • Institut Jules Bordet
  • Brussels, Belgium
    • Cliniques Universitaires Saint-luc
  • Haine St Paul, Belgium
    • Hôpital de Jolimont
  • Kortrijk, Belgium
    • AZ Groeninge Kortrijk
  • Leuven, Belgium
    • UZ Leuven
  • Liège, Belgium
    • CHU Sart-Tilman
  • Namur, Belgium
    • Clinique et Maternite Sainte Elisabeth
  • Oostende, Belgium
    • AZ Damiaan
  • Sint-Niklaas, Belgium
    • AZ Nikolaas
• France
  • Dijon, France
    • Centre Georges-Francois-Leclerc
  • Lille, France
    • Centre Oscar Lambret
  • Saint-Cloud, France
    • Hôpital René Huguenin - Institut Curie
  • Strasbourg, France
    • Centre Paul Strauss
• Italy
  • Milano, Italy
    • Istituto Europeo Di Oncologia
  • Padova, Italy
    • Istituto Oncologico Veneto IRCCS - Ospedale Busonera
• Netherlands
  • Leiden, Netherlands
    • Leiden University Medical Centre
  • Venlo, Netherlands
    • VieCuri - Medisch Centrum voor Noord-Limburg - Locatie Venlo
• Poland
  • Warsaw, Poland
    • Maria Sklodowska-Curie Memorial Cancer Centre
• Portugal
  • Lisboa, Portugal
    • Champalimaud Cancer Center
  • Lisboa, Portugal
    • Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
• Sweden
  • Goteborg, Sweden
    • Sahlgrenska Universitetssjukhuet
  • Jonkoping, Sweden
    • Ryhov County Hospital
  • Uppsala, Sweden
    • Uppsala University Hospital - Akademiska sjukhuset
  • Vasteras, Sweden
    • Vastmanland Centralsjukhuset Vasteras
• United Kingdom
  • Cardiff, United Kingdom
    • Velindre NHS Trust - Velindre Cancer Centre
  • Edinburgh, United Kingdom
    • NHS Lothian - Western General Hospital
  • Glasgow, United Kingdom
    • NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
  • Peterboroug, United Kingdom
    • Peterborough and Stamford Hospitals NHS Foundation Trust - Peterborough City Hospita
  • Southampton, United Kingdom
    • University Hospital Southampton NHS Foundation Trust - Southampton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with histologically proven HER-2 positive
• Newly diagnosed or recurrent (after surgery) stage IV disease (TNM/AJCC v.7).
• Patients must have measurable (RECIST v. 1.1) or evaluable disease
• Performance status (PS) 0-3 (WHO)
• Age ≥ 70 years of age, or ≥ 60 years old with required number of dependencies
• Life expectancy of more than 12 weeks
• Previous adjuvant chemotherapy/anti HER-2 therapy after surgery is allowed, given that the time interval from end of previous treatment to initiation of treatment for metastatic disease is ≥ 6 months.
• Up to one line of anti-HER therapy (trastuzumab or lapatinib) is allowed in combination with hormone therapy for hormone sensitive metastatic breast cancer.
• Adequate organ function
• Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

• No brain metastases that are untreated, symptomatic, or require steroids to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to the first study treatment.
• No prior chemotherapy for metastatic disease is allowed
• No prior treatment with pertuzumab is allowed
• No history of exposure to the following cumulative doses of anthracyclines:
• Doxorubicin or liposomal doxorubicin > 360 mg/m2
• Epirubicin > 720 mg/m2
• Mitoxantrone > 120 mg/m2
• Idarubicin > 90 mg/m2
• If another anthracycline or more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin.
• No history of palliative radiotherapy within 14 days of randomization
• No history of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin
• No current uncontrolled hypertension (persistent systolic > 180 mmHg and/or diastolic > 100 mmHg)
• No LVEF below 50%
• No history of significant cardiac disease defined as:
• Symptomatic CHF (NYHA classes II-IV)
• High-risk uncontrolled arrhythmias
• History of myocardial infarction within 6 months prior to randomization
• Clinically significant valvular heart disease
• No angina pectoris requiring anti-angina treatment
• No peripheral neuropathy of Grade ≥ 3 per NCI CTCAE version 4.0.
• No current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures, known infection with HIV, active hepatitis B and/or hepatitis C virus)
• No major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
• No history of receiving any investigational treatment within 28 days of randomization
• No history of intolerance (including Grade 3-4 infusion reaction) to trastuzumab
• No unwillingness or inability to comply with the requirements of the protocol as assessed by the investigator
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pertuzumab + trastuzumab (PH); Pertuzumab + trastuzumab. After progression,patients will be given the option of receiving T-DM1	Drug: Pertuzumab + trastuzumab; Trastuzumab: loading dose of 8 mg/kg of body weight on cycle 1, followed by a maintenance dose of 6 mg/kg every 3 weeks. Pertuzumab: loading dose of 840 mg on cycle 1, followed by 420 mg for subsequent cycles, every 3 weeks. if T-DM1: 3.6 mg/kg IV, every 3 weeks.
Experimental: PH + metronomic chemotherapy (PHM); Pertuzumab + trastuzumab + metronomic chemotherapy. After progression,patients will be given the option of receiving T-DM1	Drug: Pertuzumab + trastuzumab + metronomic chemotherapy; Pertuzumab and trastuzumab will be administered as in arm A. Cyclophosphamide: daily dose of 50 mg/day. if T-DM1: as in arm A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival rate	6 months after patients in

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival
Breast cancer specific survival
Tumor response rate as measured by RECIST v1.1
Evolution of HRQoL as assessed by EORTC QLQ-C30 and ELD 14	Up to 1 year after treatment start
Evolution of geriatric assessment	Up to 1 year after treatment start
if T-DM1: progression free survival rate	6 months after start of T-DM1 treatment

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: Hoffmann-La Roche
• Investigators: Study Chair: Hans Wildiers, MD, UZ Leuven, Leuven, Belgium

Publications and helpful links

General Publications

• Wildiers H, Tryfonidis K, Dal Lago L, Vuylsteke P, Curigliano G, Waters S, Brouwers B, Altintas S, Touati N, Cardoso F, Brain E. Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2-positive metastatic breast cancer (EORTC 75111-10114): an open-label, randomised, phase 2 trial from the Elderly Task Force/Breast Cancer Group. Lancet Oncol. 2018 Mar;19(3):323-336. doi: 10.1016/S1470-2045(18)30083-4. Epub 2018 Feb 9.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): November 1, 2022

Study Registration Dates

• First Submitted: May 7, 2012
• First Submitted That Met QC Criteria: May 10, 2012
• First Posted (Estimate): May 14, 2012

Study Record Updates

• Last Update Posted (Actual): November 17, 2022
• Last Update Submitted That Met QC Criteria: November 16, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab; Pertuzumab
• Other Study ID Numbers: EORTC-75111-10114; 2011-006342-32 (EudraCT Number)