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
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