Clinical trial NCT01597414: Elderly Metastatic Breast Cancer: Pertuzumab-Herceptin vs Pertuzumab-Herceptin-Metronomic Chemotherapy, Followed by T-DM1
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Elderly Metastatic Breast Cancer Population
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Hoffmann-La Roche
First posted: 2012-05-14
Enrollment: 80
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression free survival rate
timeFrame: 6 months after patients in
Secondary outcomes:
measure: Overall survival
measure: Breast cancer specific survival
measure: Tumor response rate as measured by RECIST v1.1
measure: Evolution of HRQoL as assessed by EORTC QLQ-C30 and ELD 14
timeFrame: Up to 1 year after treatment start
measure: Evolution of geriatric assessment
timeFrame: Up to 1 year after treatment start
measure: if T-DM1: progression free survival rate
timeFrame: 6 months after start of T-DM1 treatment
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: UZ Antwerpen
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Haine St Paul
country: Belgium
facility: Hopital De Jolimont
city: Kortrijk
country: Belgium
facility: AZ Groeninge Kortrijk
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHU Sart-Tilman
city: Namur
country: Belgium
facility: Clinique et Maternité Sainte Elisabeth
city: Oostende
country: Belgium
facility: AZ Damiaan
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas
city: Dijon
country: France
facility: Centre Georges-Francois-Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Saint-Cloud
country: France
facility: Hopital Rene Huguenin - Institut Curie
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS - Ospedale Busonera
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
city: Venlo
country: Netherlands
facility: VieCuri - Medisch Centrum voor Noord-Limburg - Locatie Venlo
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Centre
city: Lisboa
country: Portugal
facility: Champalimaud Cancer Center
city: Lisboa
country: Portugal
facility: Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuet
city: Jonkoping
country: Sweden
facility: Ryhov County Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital - Akademiska Sjukhuset
city: Vasteras
country: Sweden
facility: Vastmanland Centralsjukhuset Vasteras
city: Cardiff
country: United Kingdom
facility: Velindre NHS Trust - Velindre Cancer Centre
city: Edinburgh
country: United Kingdom
facility: NHS Lothian - Western General Hospital
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
city: Peterboroug
country: United Kingdom
facility: Peterborough and Stamford Hospitals NHS Foundation Trust - Peterborough City Hospita
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust - Southampton General Hospital
Study officials:
affiliation: UZ Leuven, Leuven, Belgium
name: Hans Wildiers, MD
role: STUDY_CHAIR
References:
citation: 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.