Trastuzumab Optimization Trial in Breast Cancer (TOP)

March 10, 2008 updated by: Regione Lombardia

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 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
500

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • Herceptin
No Intervention: B

In the maintenance study:

ARM B: interruption of trastuzumab treatment

In the 2nd line study:

ARM B: chemotherapy alone

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
progression free survival for maintenance study and overall survival for 2nd line study
Time Frame: 2.5 years
2.5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
overall survival for the maintenance study and progression free survival for the 2nd line study
Time Frame: 2.5 years
2.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Regione Lombardia

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Mario Negri Institute for Pharmacological Research
Istituto Clinico Humanitas

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2007

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2009

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 7, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 17, 2008

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 17, 2008

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2008

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TOP

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