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Trastuzumab Optimization Trial in Breast Cancer

Information source: Regione Lombardia
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Metastatic or Locally Advanced Breast Cancer

Intervention: trastuzumab (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Regione Lombardia

Official(s) and/or principal investigator(s):
Armando Santoro, MD, Principal Investigator, Affiliation: Istituto Clinico Humanitas

Overall contact:
Irene Floriani, PhD, Phone: +390239014695, Email: floriani@marionegri.it

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.

Clinical Details

Official title: 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.

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: progression free survival for maintenance study and overall survival for 2nd line study

Secondary outcome: overall survival for the maintenance study and progression free survival for the 2nd line study

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.

Eligibility

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Female.

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

Exclusion Criteria:

- 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 <50% (measured by echocardiography or MUGA) performed within 4 weeks

prior to randomisation. History of documented congestive heart failure, angina pectoris requiring antianginal medication, evidence of transmural infarction ECG, poorly controlled hypertension (systolic > 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 liposomal 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

Locations and Contacts

Irene Floriani, PhD, Phone: +390239014695, Email: floriani@marionegri.it

Humanitas Cliniche Gavazzeni, Bergamo 24125, Italy; Not yet recruiting
Piermario Salvini, MD, Principal Investigator

Policlinico Sant'Orsola - Malpighi, Bologna 40138, Italy; Not yet recruiting
Andrea martoni, MD, Principal Investigator

Ospedale Sant'Orsola Fatebenefratelli, Brescia 25122, Italy; Not yet recruiting
Giordano Beretta, MD, Principal Investigator

Ospedale A. Perrino, Brindisi 72021, Italy; Not yet recruiting
Saverio Cinieri, MD, Principal Investigator

Azienda Ospedaliera Sant' Anna, Como 22100, Italy; Not yet recruiting
Monica Giordano, MD, Principal Investigator

Azienda Ospedaliera Istituti Ospitalieri, Cremona 26100, Italy; Not yet recruiting
Rodolfo Passalacqua, MD, Principal Investigator

Ospedale Alessandro Manzoni, Lecco 23900, Italy; Not yet recruiting
Giovanni Ucci, MD, Principal Investigator

Azienda Ospedaliera San Paolo, Milano 20142, Italy; Not yet recruiting
Paolo Foa, MD, Principal Investigator

Fondazione San Raffaele del Monte Tabor, Milano 20133, Italy; Not yet recruiting
Eugenio Villa, MD, Principal Investigator

Istituto Europeo di Oncologia, Milano 20141, Italy; Not yet recruiting
Franco Nolè, MD, Principal Investigator

Ospedale Fatebenefratelli e Oftalmico, Milano 20121, Italy; Not yet recruiting
Gabriella Farina, MD, Principal Investigator

Azienda Ospedaliero-Universitaria di Parma, Parma 43100, Italy; Not yet recruiting
Antonio Musolino, MD, Principal Investigator

Ospedale Misericordia e Dolce - USL 4, Prato 59100, Italy; Not yet recruiting
Laura Biganzoli, MD, Principal Investigator

Dipartimento Oncologico USL 7 Siena, Siena 53100, Italy; Not yet recruiting
Sergio Crispino, MD, Principal Investigator

Ospedale Civile di Sondrio, Sondrio 23100, Italy; Not yet recruiting
Alessandro Bertolini, MD, Principal Investigator

Ospedale "Di Circolo e Fonadazione Macchi", Varese 21100, Italy; Not yet recruiting
Giovanni Giardina, MD, Principal Investigator

Ospedale E. Profili, Fabriano, Ancona 60044, Italy; Recruiting
Rosa Rita Silva, MD, Principal Investigator

Azienda Ospedaliera Treviglio- Caravaggio, Treviglio, Bergamo 24047, Italy; Not yet recruiting
Sandro Barni, MD, Principal Investigator

Policlinico Universitario, Monserrato, Cagliari 09042, Italy; Not yet recruiting
Giovanni Mantovani, MD, Principal Investigator

Istituto Clinico Humanitas, Rozzano, Milan 20089, Italy; Recruiting
Armando Santoro, MD, Principal Investigator

Azienda Ospedaliera di Melegnano - Presidio Ospedaliero di Gorgonzola, Gorgonzola, Milano 20069, Italy; Not yet recruiting
Luciano Isa, MD, Principal Investigator

Azienda Ospedaliera Ospedale San Salvatore, Pesaro, Pesaro - Urbino 61100, Italy; Not yet recruiting
Anna Maria Baldelli, MD, Principal Investigator

Ospedale Santa Croce, Fano, Pesaro-Urbino 61032, Italy; Not yet recruiting
Rodolfo Mattioli, MD, Principal Investigator

Ospedale E. Morelli, Sondalo, Sondrio 23035, Italy; Not yet recruiting
Giuseppe Valmadre, MD, Principal Investigator

Azienda Ospedaliera Busto Arsizio - Presidio ospedaliero Saronno, Saronno, Varese 21047, Italy; Not yet recruiting
Claudio Verusio, MD, Principal Investigator

Additional Information

Starting date: November 2007
Last updated: March 10, 2008

Page last updated: August 23, 2015

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