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 two 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.
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 is now closed to enrollment.
The ALTTO trial also includes an extensive translational research program to identify biomarkers.
Treatments — Design 2 only
| Duration: 52 weeks |
Concurrent Docetaxel 75 mg/m2 IV every 3 weeks (4 cycles) |
Concurrent Paclitaxel 80 mg/m2 IV weekly (12 weeks) |
| Trastuzumab only | 2 mg/kg IV* weekly for 12 weeks, then 6 mg/kg IV every 3 weeks for 40 weeks | Trastuzumab 2 mg/kg IV* weekly for 12 weeks, then 6 mg/kg IV every 3 weeks for 40 weeks |
| Lapatinib only† | 1250 mg po daily for 12 weeks, then 1500 mg po daily for 40 weeks | 1500 mg po daily for 52 weeks |
| Sequential | Trastuzumab 2 mg/kg IV* weekly for 12 weeks → 6-week washout → lapatinib 1500 mg po daily for 34 weeks | Trastuzumab 2 mg/kg IV* weekly for 12 weeks → 6-week washout → lapatinib 1500 mg po daily for 34 weeks |
| Combination† | Lapatinib 1000 mg po daily + trastuzumab 2 mg/kg IV* weekly for 12 weeks, then lapatinib 1000 mg po daily + trastuzumab 6 mg/kg IV every 3 weeks for 40 weeks | Lapatinib 750 mg po daily + trastuzumab 2 mg/kg IV* weekly for 12 weeks, then lapatinib 1000 mg po daily + trastuzumab 6 mg/kg IV every 3 weeks for 40 weeks |
|
*4 mg/kg IV loading dose. †Prophylactic G-CSF is mandatory for administration of docetaxel.  Radiotherapy and endocrine therapy permitted concomitantly with biologic therapy in all treatment arms (both designs), 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
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.
Contact Information
BIG: ALTTOtrials@bordet.be • http://www.breastinternationalgroup.orgNCCTG: altto@mayo.edu
| GlaxoSmithKline: | lapatinibtrials.northamerica@gsk.com |
| lapatinibtrials.europe@gsk.com | |
| lapatinibtrials.restoftheworld@gsk.com |
