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

NCT01597414 | Completed Phase 2 DMC

• 2 other identifiers: EORTC-75111-101142011-006342-32
• Study Type: interventional
• Target: 80
• Locations: 8 countries
• Sites: 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

Outcome Measures

Primary Outcomes (1)

• Progression free survival rate

  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

  Up to 1 year after treatment start

• Evolution of geriatric assessment

  Up to 1 year after treatment start

Study Arms (2)

Pertuzumab + trastuzumab (PH)

ACTIVE COMPARATOR

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

Drug: Pertuzumab + trastuzumab

PH + metronomic chemotherapy (PHM)

EXPERIMENTAL

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

Drug: Pertuzumab + trastuzumab + metronomic chemotherapy

Interventions

Pertuzumab + trastuzumab 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.

Pertuzumab + trastuzumab (PH)

Pertuzumab + trastuzumab + metronomic chemotherapy 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

PH + metronomic chemotherapy (PHM)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Hoffmann-La Roche: collaborator

Study Sites (30)

UZ Antwerpen

Antwerp, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Institut Jules Bordet

Brussels, Belgium

Location

Hopital De Jolimont

Haine-Saint-Paul, Belgium

Location

AZ Groeninge Kortrijk

Kortrijk, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

CHU Sart-Tilman

Liège, Belgium

Location

Clinique et Maternité Sainte Elisabeth

Namur, Belgium

Location

AZ Damiaan

Ostend, Belgium

Location

AZ Nikolaas

Sint-Niklaas, Belgium

Location

Centre Georges-Francois-Leclerc

Dijon, France

Location

Centre Oscar Lambret

Lille, France

Location

Hopital Rene Huguenin - Institut Curie

Saint-Cloud, France

Location

Centre Paul Strauss

Strasbourg, France

Location

Istituto Europeo Di Oncologia

Milan, Italy

Location

Istituto Oncologico Veneto IRCCS - Ospedale Busonera

Padua, Italy

Location

Leiden University Medical Centre

Leiden, Netherlands

Location

VieCuri - Medisch Centrum voor Noord-Limburg - Locatie Venlo

Venlo, Netherlands

Location

Maria Sklodowska-Curie Memorial Cancer Centre

Warsaw, Poland

Location

Champalimaud Cancer Center

Lisbon, Portugal

Location

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

Lisbon, Portugal

Location

Sahlgrenska Universitetssjukhuet

Gothenburg, Sweden

Location

Ryhov County Hospital

Jönköping, Sweden

Location

Uppsala University Hospital - Akademiska Sjukhuset

Uppsala, Sweden

Location

Vastmanland Centralsjukhuset Vasteras

Västerås, Sweden

Location

Velindre NHS Trust - Velindre Cancer Centre

Cardiff, United Kingdom

Location

NHS Lothian - Western General Hospital

Edinburgh, United Kingdom

Location

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

Glasgow, United Kingdom

Location

Peterborough and Stamford Hospitals NHS Foundation Trust - Peterborough City Hospita

Peterboroug, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust - Southampton General Hospital

Southampton, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29433963 DERIVED

MeSH Terms

Interventions

pertuzumab; Trastuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hans Wildiers, MD

  UZ Leuven, Leuven, Belgium

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2012
• First Posted: May 14, 2012
• Study Start: June 1, 2013
• Primary Completion: March 1, 2017
• Study Completion: November 1, 2022
• Last Updated: November 17, 2022

Record last verified: 2022-11

Locations

GB (5); PT (2); PL (1); FR (4); BE (10); NL (2); SE (4); IT (2)