Trial Overview
Study Title
A randomised, multi-centre, open-label, phase III study of adjuvant lapatinib, trastuzumab, their sequence and their combination in patients with HER2 (ErbB2)-positive primary breast cancer (Study no. BIG 2-06/N06D/EGF106708).
Study Design
The ALTTO trial is a phase III, randomised, multi-centre, open-label trial that employs three study designs. In Design 1, all (neo)adjuvant chemotherapy is completed prior to administration of the study treatments. In Design 2, all anthracycline-based (neo)adjuvant chemotherapy is completed prior to administration of the study treatments, while taxane is given concurrently with the study treatments. In Design 2B, a nonanthracycline regimen containing docetaxel and carboplatin is given concurrently with study treatments.

As shown in the study schema, within each design, patients are randomised to one of four treatment arms: 1) trastuzumab alone; 2) lapatinib alone; 3) trastuzumab followed by lapatinib; or 4) lapatinib in combination with trastuzumab.
Design 1*: All (neo)adjuvant chemotherapy is completed prior to study treatments.


*Design 1 is now closed to enrollment.

Design 2: A taxane is given concurrently with study treatments.




Design 2 is now closed to screening.

Design 2B: Nonanthracycline regimen containing docetaxel and carboplatin given concurrently with study treatments.


Available in North America only for new patient enrollment.

Study treatment will be administered for 1 year (52 weeks); patients will be followed for a total of 10 years.
Treatments: Design 2B
Duration:
52 weeks
Concurrent Docetaxel
75 mg/m2 IV and Carboplatin AUC 6 IV
every three weeks (6 doses)
Trastuzumab onlyTrastuzumab 2 mg/kg IV* weekly for 18 weeks, then 6 mg/kg IV every 3 weeks for 34 weeks
Lapatinib only750 mg po daily for 18 weeks, then 1500 mg po daily for 34 weeks
SequentialTrastuzumab 2 mg/kg IV* weekly for 18 weeks, then 6-week washout, then lapatinib 1500 mg po daily for 28 weeks
CombinationLapatinib 750 mg po daily + trastuzumab 2 mg/kg IV* weekly for 18 weeks, then lapatinib 1000 mg po daily + trastuzumab 6 mg/kg IV every 3 weeks for 34 weeks
*4 mg/kg IV loading dose.

Prophylactic G-CSF support is mandatory for all treatment arms in Design 2B during the first 18 weeks of treatment (chemotherapy concomitantly with targeted therapy).
Radiotherapy and endocrine therapy permitted concomitantly with biologic therapy in all treatment arms, if indicated.
Key Patient Eligibility Criteria
  • Histologically confirmed, nonmetastatic, primary invasive breast carcinoma
  • Adequate tumour excision and axilla dissection (if positive sentinel node)
  • Axillary node positive, or node negative with tumour ≥1 cm
  • Known ER or ER/PgR status
  • Documented overexpression and/or amplification of HER2 (ErbB2) in tumour (Central confirmation of HER2 (ErbB2) status is mandatory)
  • No prior use of anti-HER2 (ErbB2) therapy
  • Baseline LVEF ≥50%
Study Objectives
Primary

  • Compare disease-free survival (DFS) between each of the lapatinib-containing arms and the trastuzumab-alone arm

Secondary

  • Overall survival (OS)
  • Time to recurrence (TTR)
  • Time to distant recurrence (TTDR)
  • Safety and tolerability
  • Cumulative incidence of brain metastases as the first site of breast cancer recurrence
  • Conduct the above analyses according to:

  • – cMyc gene amplification
    – Expression levels of PTEN
    – p95HER2 domain
The ALTTO trial also includes an extensive translational research program to identify biomarkers.
Study Location
ALTTO is a global trial that will be conducted in 1300 sites in approximately 50 countries.
Study Status
ALTTO began enrolling patients in June 2007. The trial is now closed to enrolment (the last patient was randomised in July 2011).
                 

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