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

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase

Completed

Phase 2

Conditions

Elderly Metastatic Breast Cancer Population

Treatments

Drug: Pertuzumab + trastuzumab

Drug: Pertuzumab + trastuzumab + metronomic chemotherapy

Study type

Interventional

Funder types

NETWORK

Industry

Identifiers

NCT01597414

2011-006342-32 (EudraCT Number)

EORTC-75111-10114

Details and patient eligibility

About

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.

Enrollment

80 estimated patients

Sex

All

Ages

60+ years old

Volunteers

No Healthy Volunteers

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