Trial Information

TOP Trial. A Randomised Phase III Clinical Trial of Trastuzumab (Herceptin) Optimization in Patients With Locally Advanced and/or Metastatic Breast Cancer Overexpressing HER2 After a First Line Chemotherapy Plus Trastuzumab.

This project consists of two independent, following specific eligibility criteria and
different randomisation schemes studies, later on called maintenance study and 2nd line
study. All patients enrolled in the maintenance study, after disease progression should be
screened to enter the 2nd line study. Maintenance study: Open-label, randomised, phase III,
multicenter, Italian study designed to investigate the role of a maintenance therapy with
trastuzumab in patients with locally advanced and/or metastatic breast cancer over
expressing HER2 and not progressed to a first line chemotherapy plus trastuzumab. Patients
will be ed to: Arm A: maintenance of trastuzumab treatment Arm B: interruption of
trastuzumab treatment with a ratio 2 maintenance trastuzumab : 1 interruption of
trastuzumab. Trastuzumab will be administered intravenously once every 3 weeks until
progression of disease, unmanageable toxicity or patient refusal. Patients will be evaluated
for progression every 9 weeks (corresponding to the time required to complete the evaluation
after every 3 trastuzumab infusions). For patients whose disease has not progressed two
years after enrolment, treatment will continue according to physician decision and disease
assessments will be made following the routine clinical practice. Follow-up will be
continued until the achievement of the required number of events. 2nd line study:
Open-label, randomised, phase III, multicentre, Italian study designed to investigate the
role of a second line therapy with trastuzumab in patients with locally advanced and/or
metastatic breast cancer over expressing HER2 and progressed to a first line chemotherapy
plus trastuzumab. Patients will be randomised to: Arm A: trastuzumab + chemotherapy
treatment Arm B: chemotherapy alone with a ratio 1 trastuzumab + chemotherapy treatment : 1
chemotherapy alone. Trastuzumab will be administered intravenously, concomitant to a second
line chemotherapy of physician's choice. Trastuzumab can be given on a weekly or 3-weekly
schedule to accomplish the schedule of concomitant chemotherapy, until progression of
disease, unmanageable toxicity or patient refusal. Patients will be evaluated for
progression every 9 weeks (corresponding to the time required to complete the evaluation
after every 3 trastuzumab infusions). Follow-up will be continued until the achievement of
the required number of events. In maintenance study, trastuzumab will be given in an
outpatient setting every 3 weeks at the dose of 6 mg/Kg by intravenous infusion over 90
minutes, or over 30 minutes at the Investigator's discretion followed by 30 minutes
observation time. If the last previous dose of trastuzumab was given more than 4 weeks
before entering the study, patients will receive a re-loading dose of trastuzumab 8 mg/kg
over 90 minutes, followed by 30 minutes observation time. Therapy with trastuzumab will
continue until progression of disease, unmanageable toxicity or patient refusal. For
patients whose disease has not progressed two years after enrolment, treatment will continue
according to physician decision and disease assessments will be made following the routine
clinical practice. In 2nd line study, to accomplish the schedule of concomitant second line
chemotherapy, trastuzumab will be given on a weekly (2 mg/kg) or a 3-weekly (6 mg/kg) basis
with the modalities of the maintenance study, according to clinician's decision. Concomitant
second line chemotherapy will be left at physician's choice. If the last previous dose of
trastuzumab was given more than 4 weeks before entering the study, patients will receive a
re-loading dose of trastuzumab 4 mg/kg over 60 minutes, followed by 30 minutes observation
time.