Trial Information

Phase 1 Study of the Combination of Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast Cancer

Patients selection criteria:

- age 18 - 70 years

- Women with cytologically or histologically proven metastatic breast cancer with
recurrent / progressive brain metastases evaluable by MRI, after standard treatment
with surgery (at least 3 weeks prior) or WBRT (at least 3 weeks prior) or stereotactic
RT (at least 1 week prior); or otherwise deemed as unsuitable for standard treatment in
the first instance

- Known HER-2 positive status (immunohistochemistry (IHC) 3+ Fluorescence In Situ
Hybridization (FISH) positive )

- Previous chemotherapy (adjuvant and metastatic regimens) allowed

- Previous treatment with trastuzumab allowed (Trastuzumab to be discontinued prior to
study entry)

- At least one measurable lesion in the brain, defined as any lesion >5mm in longest
dimension on T1-weighted, gadolinium-enhanced MRI

- Expected life-expectancy of more than 3 months

- ECOG performance status of 0, 1 or 2

- Adequate bone marrow, renal and hepatic functionsLVEF

- LVEF 50% measured by echocardiography or MUGA scan

- Concomitant corticosteroids and anti-convulsants for symptomatic brain metastases are
allowed