NCT01688609

Lapatinib Ditosylate, Trastuzumab, Paclitaxel, and Surgery in Treating Patients With Breast Cancer

Phase II Study of Lapatinib and Trastuzumab Followed by Concurrent Lapatinib, Trastuzumab, and Paclitaxel Followed by Surgery for Primary HER2-positive (HER2+) Breast Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: Female
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well giving lapatinib ditosylate together with trastuzumab, paclitaxel, and surgery works in treating patients with breast cancer. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Detailed description

PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: I. To determine the cellular response rate produced by study drug exposure and/or concurrent preoperative chemotherapy. 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. OUTLINE: Drug exposure: Patients receive lapatinib ditosylate orally (PO) once daily (QD) and trastuzumab intravenously (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\* or mastectomy\*. 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.

Conditions

• HER2-positive Breast Cancer
• Stage II Breast Cancer
• Stage IIIA Breast Cancer

Interventions

Type	Name	Description
DRUG	lapatinib ditosylate	Given PO
DRUG	paclitaxel	Given IV
BIOLOGICAL	trastuzumab	Given IV
PROCEDURE	therapeutic conventional surgery	Undergo lumpectomy or mastectomy
OTHER	pharmacological study	Correlative studies
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2012-07-01
• Primary completion: 2013-12-01
• Completion: 2016-08-15
• First posted: 2012-09-20
• Last updated: 2017-09-11
• Results posted: 2017-09-11

Locations

3 sites across 2 countries: United States, Japan