Trastuzumab Optimization Trial in Breast Cancer (TOP)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2008 by Regione Lombardia.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Mario Negri Institute for Pharmacological Research
Istituto Clinico Humanitas
Information provided by:
Regione Lombardia
ClinicalTrials.gov Identifier:
NCT00637325
First received: March 7, 2008
Last updated: March 10, 2008
Last verified: March 2008
  Purpose

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.


Condition Intervention Phase
Metastatic or Locally Advanced Breast Cancer
Drug: trastuzumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Regione Lombardia:

Primary Outcome Measures:
  • progression free survival for maintenance study and overall survival for 2nd line study [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • overall survival for the maintenance study and progression free survival for the 2nd line study [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 500
Study Start Date: November 2007
Estimated Study Completion Date: April 2011
Estimated Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A

In the maintenance study:

ARM A: maintenance of trastuzumab

In the 2nd line study:

ARM A: trastuzumab plus chemotherapy treatment

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).
Other Name: Herceptin
No Intervention: B

In the maintenance study:

ARM B: interruption of trastuzumab treatment

In the 2nd line study:

ARM B: chemotherapy alone


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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00637325

Contacts
Contact: Irene Floriani, PhD +390239014695 floriani@marionegri.it

Locations
Italy
Ospedale E. Profili Recruiting
Fabriano, Ancona, Italy, 60044
Principal Investigator: Rosa Rita Silva, MD         
Azienda Ospedaliera Treviglio- Caravaggio Not yet recruiting
Treviglio, Bergamo, Italy, 24047
Principal Investigator: Sandro Barni, MD         
Policlinico Universitario Not yet recruiting
Monserrato, Cagliari, Italy, 09042
Principal Investigator: Giovanni Mantovani, MD         
Azienda Ospedaliera di Melegnano - Presidio Ospedaliero di Gorgonzola Not yet recruiting
Gorgonzola, Milano, Italy, 20069
Principal Investigator: Luciano Isa, MD         
Istituto Clinico Humanitas Recruiting
Rozzano, Milan, Italy, 20089
Principal Investigator: Armando Santoro, MD         
Azienda Ospedaliera Ospedale San Salvatore Not yet recruiting
Pesaro, Pesaro - Urbino, Italy, 61100
Principal Investigator: Anna Maria Baldelli, MD         
Ospedale Santa Croce Not yet recruiting
Fano, Pesaro-Urbino, Italy, 61032
Principal Investigator: Rodolfo Mattioli, MD         
Ospedale E. Morelli Not yet recruiting
Sondalo, Sondrio, Italy, 23035
Principal Investigator: Giuseppe Valmadre, MD         
Azienda Ospedaliera Busto Arsizio - Presidio ospedaliero Saronno Not yet recruiting
Saronno, Varese, Italy, 21047
Principal Investigator: Claudio Verusio, MD         
Humanitas Cliniche Gavazzeni Not yet recruiting
Bergamo, Italy, 24125
Principal Investigator: Piermario Salvini, MD         
Policlinico Sant'Orsola - Malpighi Not yet recruiting
Bologna, Italy, 40138
Principal Investigator: Andrea martoni, MD         
Ospedale Sant'Orsola Fatebenefratelli Not yet recruiting
Brescia, Italy, 25122
Principal Investigator: Giordano Beretta, MD         
Ospedale A. Perrino Not yet recruiting
Brindisi, Italy, 72021
Principal Investigator: Saverio Cinieri, MD         
Azienda Ospedaliera Sant' Anna Not yet recruiting
Como, Italy, 22100
Principal Investigator: Monica Giordano, MD         
Azienda Ospedaliera Istituti Ospitalieri Not yet recruiting
Cremona, Italy, 26100
Principal Investigator: Rodolfo Passalacqua, MD         
Ospedale Alessandro Manzoni Not yet recruiting
Lecco, Italy, 23900
Principal Investigator: Giovanni Ucci, MD         
Azienda Ospedaliera San Paolo Not yet recruiting
Milano, Italy, 20142
Principal Investigator: Paolo Foa, MD         
Ospedale Fatebenefratelli e Oftalmico Not yet recruiting
Milano, Italy, 20121
Principal Investigator: Gabriella Farina, MD         
Fondazione San Raffaele del Monte Tabor Not yet recruiting
Milano, Italy, 20133
Principal Investigator: Eugenio Villa, MD         
Istituto Europeo di Oncologia Not yet recruiting
Milano, Italy, 20141
Principal Investigator: Franco Nolè, MD         
Azienda Ospedaliero-Universitaria di Parma Not yet recruiting
Parma, Italy, 43100
Principal Investigator: Antonio Musolino, MD         
Ospedale Misericordia e Dolce - USL 4 Not yet recruiting
Prato, Italy, 59100
Principal Investigator: Laura Biganzoli, MD         
Dipartimento Oncologico USL 7 Siena Not yet recruiting
Siena, Italy, 53100
Principal Investigator: Sergio Crispino, MD         
Ospedale Civile di Sondrio Not yet recruiting
Sondrio, Italy, 23100
Principal Investigator: Alessandro Bertolini, MD         
Ospedale "Di Circolo e Fonadazione Macchi" Not yet recruiting
Varese, Italy, 21100
Principal Investigator: Giovanni Giardina, MD         
Sponsors and Collaborators
Regione Lombardia
Mario Negri Institute for Pharmacological Research
Istituto Clinico Humanitas
Investigators
Principal Investigator: Armando Santoro, MD Istituto Clinico Humanitas
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00637325     History of Changes
Other Study ID Numbers: TOP
Study First Received: March 7, 2008
Last Updated: March 10, 2008
Health Authority: Italy: AIFA Agenzia Italiana per il Farmaco

Keywords provided by Regione Lombardia:
trastuzumab optimization in breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014