Women with locally advanced or metastatic breast cancer over expressing HER2 who have been previously treated with a first line chemotherapy plus trastuzumab. MedDRA version: 9.1 Level: LLT Classification code 10006279 Term: Breast neoplasm
Conditions
Interventions
Trade Name: HERCEPTIN
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Trastuzumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 21-
Sponsors
REGIONE LOMBARDIA - DIREZIONE GENERALE SANITA'
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria:  >18 years of age. Patients older of 70 years of age are eligible on the basis of an individual risk-benefit assessment by the investigator  Histologically confirmed breast cancer with locally advanced and/or metastatic disease  Over expression of HER2 (3+) as determined by IHC or amplification of HER2/c-erbB2 by FISH/CISH of the primary tumour or of a metastasis  Assessable disease. The presence of measurable disease is not needed for enrolment. Patients with bone lesions, ascites and pleural effusion as only sites of disease are considered eligible  Completion of a first line chemotherapy in association with trastuzumab given for at least 6 months for advanced disease. The last dose of trastuzumab should have to be given within 6 weeks prior to randomisation for treatments given with a 3 weekly schedule or within 3 weeks if a weekly schedule was used (only for maintenance study)  Progressive disease during or within 6 months from the completion of a first line chemotherapy plus trastuzumab for advanced disease or within 6 months from the completion of an adjuvant treatment for early disease (only for 2nd line study). Patients progressing more than 6 months after the completion of a first line trastuzumab-containing regimen should be re-treated with the previous regimen and included in 2nd line study after evidence of progression.  Signed written informed consent obtained prior to any study specific study procedures Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Women with locally advanced or metastatic breast cancer over expressing HER2 who have been previously treated with a first line chemotherapy plus trastuzumab.  >18 years of age. Patients older of 70 years of age are eligible on the basis of an individual risk-benefit assessment by the investigator  Histologically confirmed breast cancer with locally advanced and/or metastatic disease  Over expression of HER2 (3+) as determined by IHC or amplification of HER2/c-erbB2 by FISH/CISH of the primary tumour or of a metastasis  Assessable disease. The presence of measurable disease is not needed for enrolment. Patients with bone lesions, ascites and pleural effusion as only sites of disease are considered eligible  Completion of a first line chemotherapy in association with trastuzumab given for at least 6 months for advanced disease. The last dose of trastuzumab should have to be given within 6 weeks prior to randomisation for treatments given with a 3 weekly schedule or within 3 weeks if a weekly schedule was used (only for maintenance study)  Progressive disease during or within 6 months from the completion of a first line chemotherapy plus trastuzumab for advanced disease or within 6 months from the completion of an adjuvant treatment for early disease (only for 2nd line study). Patients progressing more than 6 months after the completion of a first line trastuzumab-containing regimen should be re-treated with the previous regimen and included in 2nd line study after evidence of progression.  Signed written informed consent obtained prior to any study specific study procedures  ECOG-PS >2  Pregnant or lactating women. Women of childbearing potential must implement adequate contraceptive measures  Previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma of the skin, or other cancer curatively treated by surgery and with no evidence of disease for at least 5 years.  Baseline LVEF 180 mmHg or diastolic > 100 mmHg); clinically significant valvular heart disease; high-risk uncontrolled arrhythmias  Presence of CNS metastases, not amenable to curative therapy. Patients with previously treated CNS metastases must be asymptomatic and stable at radiological imaging from at least 3 months  Patients with dyspnoea at rest due to malignant or other disease, or who require supportive oxygen therapy. Patients with pre-existing lung disease or advanced pulmonary involvement may be at increased risk of serious toxicities with trastuzumab and should be evaluated carefully before entry into the study  Concomitant chemotherapy with anthracyclines, including liposomial drugs (only for 2nd line study)  Treatment with any investigational drug within 30 days before beginning of enrolment in the trial  History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of trastuzumab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective:  To assess whether a maintenance therapy with trastuzumab is superior in terms of PFS to no further trastuzumab treatment in patients with locally advanced and/or metastatic breast cancer over expressing HER2 and not progressed to a first line chemotherapy containing trastuzumab (maintenance study)  To assess whether a second line chemotherapy with trastuzumab after failure of a first line regimen of chemotherapy plus trastuzumab is superior in terms of OS to chemotherapy alone in patients with locally advanced and/or metastatic breast cancer over expressing HER2 (2nd line study);Secondary Objective:  To assess whether a maintenance therapy with trastuzumab is superior in terms of OS to no further trastuzumab treatment in patients with locally advanced and/or metastatic breast cancer over expressing HER2 and not progressed to a first line chemotherapy containing trastuzumab (maintenance study) To assess whether a second line chemotherapy with trastuzumab after failure of a first line regimen of chemotherapy plus trastuzumab is superior in terms of PFS to chemotherapy alone in patients with locally advanced and/or metastatic breast cancer over expressing HER2 (2nd line study) To evaluate the safety profiles of the treatments;Primary end point(s):  PFS is defined as the time from the date of randomisation up to the date of first progression, second primary malignancy or death from any cause, whichever comes first. Subjects who have not progressed or died while on study will be censored at the last disease assessment date.  OS is defined as the time from the date of randomisation to the date of death from any cause. Subjects who were not reported as having died at the time of the analysis will be censored at the date they were last known to be alive.  Toxicity, graded according to the NCI-CTAE version 3.0  Frequency and nature of serious adverse reactions  Prema | — |
Countries
Italy
Outcome results
None listed