Elderly Metastatic Breast Cancer: Pertuzumab-Herceptin vs Pertuzumab-Herceptin-Metronomic Chemotherapy, Followed by T-DM1
- Conditions
- Elderly Metastatic Breast Cancer Population
- Interventions
- Registration Number
- NCT01597414
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PH + metronomic chemotherapy (PHM) Pertuzumab + trastuzumab + metronomic chemotherapy Pertuzumab + trastuzumab + metronomic chemotherapy. After progression,patients will be given the option of receiving T-DM1 Pertuzumab + trastuzumab (PH) Pertuzumab + trastuzumab Pertuzumab + trastuzumab. After progression,patients will be given the option of receiving T-DM1
- Primary Outcome Measures
Name Time Method Progression free survival rate 6 months after patients in
- Secondary Outcome Measures
Name Time Method Overall 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 if T-DM1: progression free survival rate 6 months after start of T-DM1 treatment Breast cancer specific survival Evolution of geriatric assessment Up to 1 year after treatment start
Trial Locations
- Locations (30)
Champalimaud Cancer Center
🇵🇹Lisboa, Portugal
Centre Paul Strauss
🇫🇷Strasbourg, France
VieCuri - Medisch Centrum voor Noord-Limburg - Locatie Venlo
🇳🇱Venlo, Netherlands
Istituto Europeo Di Oncologia
🇮🇹Milano, Italy
Istituto Oncologico Veneto IRCCS - Ospedale Busonera
🇮🇹Padova, Italy
NHS Lothian - Western General Hospital
🇬🇧Edinburgh, United Kingdom
Ryhov County Hospital
🇸🇪Jonkoping, Sweden
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
UZ Antwerpen
🇧🇪Antwerpen, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Hopital De Jolimont
🇧🇪Haine St Paul, Belgium
Institut Jules Bordet
🇧🇪Brussels, Belgium
Clinique et Maternité Sainte Elisabeth
🇧🇪Namur, Belgium
AZ Groeninge Kortrijk
🇧🇪Kortrijk, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
CHU Sart-Tilman
🇧🇪Liège, Belgium
AZ Damiaan
🇧🇪Oostende, Belgium
AZ Nikolaas
🇧🇪Sint-Niklaas, Belgium
Hopital Rene Huguenin - Institut Curie
🇫🇷Saint-Cloud, France
Centre Georges-Francois-Leclerc
🇫🇷Dijon, France
Leiden University Medical Centre
🇳🇱Leiden, Netherlands
Maria Sklodowska-Curie Memorial Cancer Centre
🇵🇱Warsaw, Poland
Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
🇵🇹Lisboa, Portugal
Sahlgrenska Universitetssjukhuet
🇸🇪Goteborg, Sweden
Uppsala University Hospital - Akademiska Sjukhuset
🇸🇪Uppsala, Sweden
Velindre NHS Trust - Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
Vastmanland Centralsjukhuset Vasteras
🇸🇪Vasteras, Sweden
NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
🇬🇧Glasgow, United Kingdom
Centre Oscar Lambret
🇫🇷Lille, France