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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by European Organisation for Research and Treatment of Cancer - EORTC
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT01597414
First received: May 7, 2012
Last updated: September 26, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Elderly Metastatic Breast Cancer Population
Drug: Pertuzumab + trastuzumab
Drug: Pertuzumab + trastuzumab + metronomic chemotherapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Progression free survival rate [ Time Frame: 6 months after patients in ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Breast cancer specific survival [ Designated as safety issue: No ]
  • Tumor response rate as measured by RECIST v1.1 [ Designated as safety issue: No ]
  • Evolution of HRQoL as assessed by EORTC QLQ-C30 and ELD 14 [ Time Frame: Up to 1 year after treatment start ] [ Designated as safety issue: No ]
  • Evolution of geriatric assessment [ Time Frame: Up to 1 year after treatment start ] [ Designated as safety issue: No ]
  • if T-DM1: progression free survival rate [ Time Frame: 6 months after start of T-DM1 treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: June 2013
Arms Assigned Interventions
Active Comparator: Pertuzumab + trastuzumab (PH)
Pertuzumab + trastuzumab. After progression,patients will be given the option of receiving T-DM1
Drug: 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.

Experimental: PH + metronomic chemotherapy (PHM)
Pertuzumab + trastuzumab + metronomic chemotherapy. After progression,patients will be given the option of receiving T-DM1
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

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01597414

Contacts
Contact: Nicolas Dif, PhD +32 2 774 10 43 nicolas.dif@eortc.be

Locations
Belgium
UZ Antwerpen Recruiting
Antwerpen, Belgium
Principal Investigator: Sevilay Altintas         
Cliniques Universitaires Saint-Luc Recruiting
Brussels, Belgium
Principal Investigator: Franck Cornelis         
Institut Jules Bordet Recruiting
Brussels, Belgium
Principal Investigator: Lissandra Dal Lago         
Hopital De Jolimont Recruiting
Haine St Paul, Belgium
Principal Investigator: Bénédicte Petit         
UZ Leuven Recruiting
Leuven, Belgium
Principal Investigator: Hans Wildiers         
CHU Sart-Tilman Recruiting
Liège, Belgium
Principal Investigator: Guy Jerusalem         
Clinique et Maternité Sainte Elisabeth Recruiting
Namur, Belgium
Principal Investigator: Peter Vuylsteke         
AZ Damiaan Recruiting
Oostende, Belgium
Principal Investigator: Randal D'hondt         
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Hoffmann-La Roche
Investigators
Study Chair: Hans Wildiers, MD UZ Leuven, Leuven, Belgium
  More Information

No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT01597414     History of Changes
Other Study ID Numbers: EORTC-75111-10114, 2011-006342-32
Study First Received: May 7, 2012
Last Updated: September 26, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Pertuzumab
Trastuzumab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014