Phase II Study of Lapatinib and Trastuzumab Followed by Concurrent Lapatinib, Trastuzumab, and Paclitaxel Followed by Surgery for Primary HER2-positive (HER2+) Breast Cancer
I. To evaluate the changes in cancer stem cell (CSC) markers; % CD44 variant
(CD44v)-positive tumor cells and aldehyde dehydrogenase-1 (ALDH1) positivity before and
after study drug exposure and after concurrent preoperative chemotherapy.
II. To determine the pathological complete response (pCR) rate produced by lapatinib
(lapatinib ditosylate) + trastuzumab followed by concurrent preoperative lapatinib,
trastuzumab, and paclitaxel chemotherapy for operable human epidermal growth factor receptor
2-positive (HER2+) breast cancer.
I. To determine the cellular response rate produced by study drug exposure and/or concurrent
II. To determine cutoff values of baseline ratios of phosphorylated HER2 (pHER2)/HER2,
phosphorylated epidermal growth factor receptor (EGFR) (pEGFR)/EGFR, phosphorylated ERK
(pERK)/ERK and phosphorylated protein kinase B (pAkt)/Akt that are associated with pCR.
III. To assess the safety and tolerability of study therapy in Japanese women.
Drug exposure: Patients receive lapatinib ditosylate orally (PO) once daily (QD) and
trastuzumab IV over 30-90 minutes once weekly for 6 weeks in the absence of disease
progression or unacceptable toxicity.
Preoperative therapy: Patients receive lapatinib ditosylate PO QD, trastuzumab IV over 30
minutes once weekly, and paclitaxel IV over 90 minutes once weekly for 12 weeks in the
absence of disease progression or unacceptable toxicity. Patients then undergo lumpectomy*
After completion of study treatment, patients are followed up for 12 weeks.
NOTE: * Patients considered to be candidates for breast-conservation therapy (BCT) are
offered lumpectomy. Patients who are not considered to be candidates for BCT or who do not
desire BCT undergo total mastectomy.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Expression of ALDH1 and CD44v change in quick score Q from baseline to 6 weeks and 18 weeks
For biomarkers ALDH1 and CD44v, the change in quick score Q from baseline to 6 weeks and 18 weeks time points will be calculated for each patient. For biomarker change pre- vs. post-treatment, a paired t-test will be used to examine whether the mean quick score has decreased significantly after the treatment. Descriptive statistics (mean, standard deviation, quartiles) will be summarized for the change in quick score post-treatment. We will also graphically present the mean ALDH1 and CD44 values at baseline, at 6 week, and at 18 week time points.
From baseline to 18 weeks
Saint Luke's International Hospital
United States: Food and Drug Administration