Elderly Metastatic Breast Cancer PopulationPhase 2NCT01597414

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

A Phase 2 study testing Pertuzumab + trastuzumab and Pertuzumab + trastuzumab + metronomic chemotherapy in people with Elderly Metastatic Breast Cancer Population, run by European Organisation for Research and Treatment of Cancer - EORTC at 30 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 60 years and older
Conditions the study is for: Elderly Metastatic Breast Cancer Population
What is being tested?: Pertuzumab + trastuzumab and Pertuzumab + trastuzumab + metronomic chemotherapy
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 80 participants
Where: 30 sitesin 8 countries
Study dates: Jun 2013to Nov 2022
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 60 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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.

Who cannot join

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

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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

Trial locations and contacts

30 sites in 8 countries.

Country

City, postcode or hospital

30 sites in 8 countries

Belgium10 sites

UZ Antwerpen
Antwerp
Cliniques Universitaires Saint-Luc
Brussels
Institut Jules Bordet
Brussels
Hopital De Jolimont
Haine-Saint-Paul
AZ Groeninge Kortrijk
Kortrijk
UZ Leuven
Leuven
CHU Sart-Tilman
Liège
Clinique et Maternité Sainte Elisabeth
Namur
AZ Damiaan
Ostend
AZ Nikolaas
Sint-Niklaas

Other trials in Belgium

United Kingdom5 sites

Velindre NHS Trust - Velindre Cancer Centre
Cardiff
NHS Lothian - Western General Hospital
Edinburgh
NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
Glasgow
Peterborough and Stamford Hospitals NHS Foundation Trust - Peterborough City Hospita
Peterboroug
University Hospital Southampton NHS Foundation Trust - Southampton General Hospital
Southampton

Other trials in United Kingdom

France4 sites

Centre Georges-Francois-Leclerc
Dijon
Centre Oscar Lambret
Lille
Hopital Rene Huguenin - Institut Curie
Saint-Cloud
Centre Paul Strauss
Strasbourg

Other trials in France

Sweden4 sites

Sahlgrenska Universitetssjukhuet
Gothenburg
Ryhov County Hospital
Jönköping
Uppsala University Hospital - Akademiska Sjukhuset
Uppsala
Vastmanland Centralsjukhuset Vasteras
Västerås

Other trials in Sweden

Italy2 sites

Istituto Europeo Di Oncologia
Milan
Istituto Oncologico Veneto IRCCS - Ospedale Busonera
Padova

Other trials in Italy

Netherlands2 sites

Leiden University Medical Centre
Leiden
VieCuri - Medisch Centrum voor Noord-Limburg - Locatie Venlo
Venlo

Other trials in Netherlands

Portugal2 sites

Champalimaud Cancer Center
Lisbon
Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
Lisbon

Other trials in Portugal

Poland1 site

Maria Sklodowska-Curie Memorial Cancer Centre
Warsaw

Other trials in Poland

About this study

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

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
Being tested: Pertuzumab + trastuzumab, Pertuzumab + trastuzumab + metronomic chemotherapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT01597414
Study group	Role	What they receive
Pertuzumab + trastuzumab (PH)	Active comparator	Pertuzumab + trastuzumab. After progression,patients will be given the option of receiving T-DM1 Receives: Drug: Pertuzumab + trastuzumab
PH + metronomic chemotherapy (PHM)	Experimental	Pertuzumab + trastuzumab + metronomic chemotherapy. After progression,patients will be given the option of receiving T-DM1 Receives: Drug: Pertuzumab + trastuzumab + metronomic chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression free survival rate
Measured: 6 months after patients in

Secondary outcomes (6)

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
Measured: Up to 1 year after treatment start
Evolution of geriatric assessment
Measured: Up to 1 year after treatment start
if T-DM1: progression free survival rate
Measured: 6 months after start of T-DM1 treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2013Nov 2022

First posted14 May 2012 (estimated)
Study startJun 2013
Primary completionMar 2017
Study completionNov 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Elderly Metastatic Breast Cancer PopulationStudies of the same condition, open and under way.
More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 80 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01597414
Sponsor's protocol ID: EORTC-75111-10114
Other IDs: 2011-006342-32
Status last verified: Nov 2022
First submitted: 7 May 2012
Last updated: 17 Nov 2022
Results posted: No
Data monitoring committee: Yes

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.
PubMed 29433963

Study at a glance

From the registry record, last updated by the sponsor on 17 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01597414
Acronym / sponsor ID: EORTC-75111-10114
Conditions: Elderly Metastatic Breast Cancer Population
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 80 participants (estimated)
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTCResearch network
Collaborators: Hoffmann-La Roche
Study start: Jun 2013
Primary completion: Mar 2017 (actual)
Study completion: Nov 2022 (actual)
First posted: 14 May 2012 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Pertuzumab + trastuzumab (PH)	Active comparator	Drug: Pertuzumab + trastuzumabPertuzumab + trastuzumab. After progression,patients will be given the option of receiving T-DM1
PH + metronomic chemotherapy (PHM)	Experimental	Drug: Pertuzumab + trastuzumab + metronomic chemotherapyPertuzumab + trastuzumab + metronomic chemotherapy. After progression,patients will be given the option of receiving T-DM1

Who may qualify

Ages: 60 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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

Key exclusion criteria (26 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Pertuzumab + trastuzumabTrastuzumab: 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.	Drug	Pertuzumab + trastuzumab (PH)
Pertuzumab + trastuzumab + metronomic chemotherapyPertuzumab and trastuzumab will be administered as in arm A. Cyclophosphamide: daily dose of 50 mg/day. if T-DM1: as in arm A	Drug	PH + metronomic chemotherapy (PHM)

Primary outcome

Progression free survival rate
Time frame: 6 months after patients in

6 secondary outcomes

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
Time frame: Up to 1 year after treatment start
Evolution of geriatric assessment
Time frame: Up to 1 year after treatment start
if T-DM1: progression free survival rate
Time frame: 6 months after start of T-DM1 treatment

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2022.
Derived from this study: PubMed 29433963Wildiers 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Hans Wildiers, MD study chair

UZ Leuven, Leuven, Belgium

30 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in Belgium, United Kingdom, France, Sweden, Italy and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival rate (time frame: 6 months after patients in). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01597414, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2022.