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

NCT ID: NCT01597414

Last Updated: 2022-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2022-11-30

Brief Summary

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.

Conditions

Elderly Metastatic Breast Cancer Population

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pertuzumab + trastuzumab (PH)

Pertuzumab + trastuzumab. After progression,patients will be given the option of receiving T-DM1

Group Type: ACTIVE_COMPARATOR

Pertuzumab + trastuzumab

Intervention Type: DRUG

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.

PH + metronomic chemotherapy (PHM)

Pertuzumab + trastuzumab + metronomic chemotherapy. After progression,patients will be given the option of receiving T-DM1

Group Type: EXPERIMENTAL

Pertuzumab + trastuzumab + metronomic chemotherapy

Intervention Type: DRUG

Pertuzumab and trastuzumab will be administered as in arm A. Cyclophosphamide: daily dose of 50 mg/day. if T-DM1: as in arm A

Interventions

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.

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hans Wildiers, MD

Role: STUDY_CHAIR

UZ Leuven, Leuven, Belgium

Locations

Sahlgrenska Universitetssjukhuet

Gothenburg, , Sweden

Ryhov County Hospital

Jönköping, , Sweden

Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.

Lisbon, , Portugal

UZ Antwerpen

Antwerp, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Hopital De Jolimont

Haine-Saint-Paul, , Belgium

AZ Groeninge Kortrijk

Kortrijk, , Belgium

UZ Leuven

Leuven, , Belgium

CHU Sart-Tilman

Liège, , Belgium

Clinique et Maternité Sainte Elisabeth

Namur, , Belgium

AZ Damiaan

Ostend, , Belgium

AZ Nikolaas

Sint-Niklaas, , Belgium

Centre Georges-Francois-Leclerc

Dijon, , France

Centre Oscar Lambret

Lille, , France

Hopital Rene Huguenin - Institut Curie

Saint-Cloud, , France

Centre Paul Strauss

Strasbourg, , France

Istituto Europeo Di Oncologia

Milan, , Italy

Istituto Oncologico Veneto IRCCS - Ospedale Busonera

Padua, , Italy

Leiden University Medical Centre

Leiden, , Netherlands

VieCuri - Medisch Centrum voor Noord-Limburg - Locatie Venlo

Venlo, , Netherlands

Maria Sklodowska-Curie Memorial Cancer Centre

Warsaw, , Poland

Champalimaud Cancer Center

Lisbon, , Portugal

Uppsala University Hospital - Akademiska Sjukhuset

Uppsala, , Sweden

Vastmanland Centralsjukhuset Vasteras

Västerås, , Sweden

Velindre NHS Trust - Velindre Cancer Centre

Cardiff, , United Kingdom

NHS Lothian - Western General Hospital

Edinburgh, , United Kingdom

NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital

Glasgow, , United Kingdom

Peterborough and Stamford Hospitals NHS Foundation Trust - Peterborough City Hospita

Peterboroug, , United Kingdom

University Hospital Southampton NHS Foundation Trust - Southampton General Hospital

Southampton, , United Kingdom

Countries

Belgium; France; Italy; Netherlands; Poland; Portugal; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 29433963 (View on PubMed)

Other Identifiers

2011-006342-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EORTC-75111-10114

Identifier Type: -

Identifier Source: org_study_id