Lapatinib +/- Trastuzumab In Addition To Standard Neoadjuvant Breast Cancer Therapy.

Summary

This study will examine safety and efficacy of Lapatinib in combination with a standard neoadjuvant chemotherapy including 5FU, Epirubicin, Cyclophosphamide and Paclitaxel. Tumor tissue will be obtained at 3 timepoints (optional 4th) to evaluate tumor response to treatment.

Timeline

Start

2007-08

Primary completion

2010-10

Completion

2015-08

Outcome

Missed primary endpoint

registry analysis (superiority or other test); Trastuzumab vs Trastuzumab+Lapatinib; Percent difference 20 (95% CI -8.0 to 49.4) NCT00524303 ↗

registry analysis (superiority or other test); Trastuzumab vs Lapatinib; Percent difference -9 (95% CI -38.1 to 17.9) NCT00524303 ↗

Publications

• O'Shea J, Cremona M, Morgan C, Milewska M, Holmes F, Espina V, Liotta L, O'Shaughnessy J, Toomey S, Madden SF, Carr A, Elster N, Hennessy BT, Eustace AJ. A preclinical evaluation of the MEK inhibitor refametinib in HER2-positive breast cancer cell lines including those with acquired resistance to trastuzumab or lapatinib. Oncotarget. 2017 Jul 22;8(49):85120-85135. doi: 10.18632/oncotarget.19461. eCollection 2017 Oct 17.
• Holmes FA, Espina V, Liotta LA, Nagarwala YM, Danso M, McIntyre KJ, Osborne CR, Anderson T, Krekow L, Blum JL, Pippen J, Florance A, Mahoney J, O'Shaughnessy JA. Pathologic complete response after preoperative anti-HER2 therapy correlates with alterations in PTEN, FOXO, phosphorylated Stat5, and autophagy protein signaling. BMC Res Notes. 2013 Dec 5;6:507. doi: 10.1186/1756-0500-6-507.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Lapatinib	Small molecule	1000 mg	Oral
Subject	Lapatinib	Small molecule	1250 mg	Oral
Subject	Trastuzumab	Monoclonal antibody	2 mg/kg	Intravenous
Background	Cyclophosphamide	Other / unclassified	500 mg/m2	Intravenous
Background	Epirubicin	Small molecule	75 mg/m2	Intravenous
Background	Paclitaxel	Small molecule	80 mg/m2	Intravenous
Background	fluorouracil	Small molecule	500 mg/m2	Intravenous

Indications