NCT00637325

Trastuzumab Optimization Trial in Breast Cancer

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.

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 500 (estimated)
• Sponsor: Regione Lombardia · Academic / Other
• Sex: Female
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, randomised phase III, multicentre, Italian study designed to investigate the role of trastuzumab in patients with locally advanced and/or metastatic breast cancer over expressing HER2 who received a first line chemotherapy containing trastuzumab. The trial in divided in two studies: 1. The maintenance study will be conducted in patients not progressing to a first line chemotherapy plus trastuzumab. 2. The 2nd line study will be conducted in patients progressing to a first line chemotherapy plus trastuzumab.

Detailed description

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.

Conditions

• Metastatic or Locally Advanced Breast Cancer

Interventions

Type	Name	Description
DRUG	trastuzumab	In the maintenance study trastuzumab will be administrated once every 3 weeks at the dose of 6 mg/kg by intravenous infusion over 90 minutes until progression of disease. In the 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).

Timeline

• Start date: 2007-11-01
• Primary completion: 2009-05-01
• Completion: 2011-04-01
• First posted: 2008-03-17
• Last updated: 2008-03-17

Locations

25 sites across 1 country: Italy