Lapatinib Ditosylate, Trastuzumab, Paclitaxel, and Surgery in Treating Patients With Breast Cancer
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|ClinicalTrials.gov Identifier: NCT01688609|
Recruitment Status : Completed
First Posted : September 20, 2012
Results First Posted : September 11, 2017
Last Update Posted : September 11, 2017
|Condition or disease||Intervention/treatment||Phase|
|HER2-positive Breast Cancer Stage II Breast Cancer Stage IIIA Breast Cancer||Drug: lapatinib ditosylate Drug: paclitaxel Biological: trastuzumab Procedure: therapeutic conventional surgery Other: pharmacological study Other: laboratory biomarker analysis||Phase 2|
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 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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Lapatinib and Trastuzumab Followed by Concurrent Lapatinib, Trastuzumab, and Paclitaxel Followed by Surgery for Primary HER2-positive (HER2+) Breast Cancer|
|Study Start Date :||July 2012|
|Actual Primary Completion Date :||December 2013|
|Actual Study Completion Date :||August 15, 2016|
Experimental: Treatment (lapatinib, trastuzumab, paclitaxel, surgery)
Drug exposure: Patients receive lapatinib ditosylate PO 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 or mastectomy.
Drug: lapatinib ditosylate
Procedure: therapeutic conventional surgery
Undergo lumpectomy or mastectomy
Other: pharmacological study
Other Name: pharmacological studies
Other: laboratory biomarker analysis
- Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks [ Time Frame: From baseline to 18 weeks ]For biomarkers ALDH1 and CD44v, the change in the proportions of CD44v-positive (CD44v+) tumor cells and ALDH1-positive (ALDH1+) tumor cells in tumor tissue from baseline to 6 weeks and 18 weeks time points were determined for each patient. For biomarker change, changes in the binary biomarkers between time points were assessed using McNemar's test in all patients and separately in patients with and without pCR.
- Number of Participants With Pathological Complete Response (pCR) [ Time Frame: Up to 12 weeks ]The point estimate of the pCR rate will be calculated for all patients. pCR is defined as the abscence of invasive cancer in the breast and regional lymph nodes following neoadjuvant chemotherapy.
- Cellular Response Rate, Defined as Patients With an Epithelial Phenotype Having Eradication of CTCs; Patients With a Mesenchymal Phenotype Having Eradication of Tumor Cells; Patients With a Mesenchymal Phenotype Converting to an Epithelial Phenotype [ Time Frame: Up to 18 weeks ]Cellular response will be documented and calculated for rate in all patients.
- EGFR-mutation Status of Tumors and Changes in the Ratio of Phosphorylated to Nonphosphorylated HER2, EGFR, ERK, Akt, and the Ki67 and TUNEL Indices Before and After Treatment [ Time Frame: From baseline to 24 weeks ]The EGFR mutation status will be a binary variable (yes vs. no), and the phosphorylation status of HER2 and EGFR will be a ratio variable (0-100%). The CART method to identify cut-off points for the phosphorylation ratio of molecules of interest will be used, such that ratios above the cut-off point will be considered "high phosphorylation" and ratios below the cut-off point will be considered "low phosphorylation."
- Number of Participants With Treatment-Related Toxicities [ Time Frame: Up to 12 weeks after completion of study treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01688609
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Shinjuku-ku, Tokyo, Japan, 160-8582|
|Saint Luke's International Hospital|
|Chuo-ku, Toyko, Japan, 104-8560|
|Principal Investigator:||Teruo Yamauchi||Saint Luke's International Hospital|