A Phase 2 interventional study of lapatinib ditosylate and paclitaxel in HER2-positive Breast Cancer, Stage II Breast Cancer and Stage IIIA Breast Cancer, sponsored by National Cancer Institute (NCI). Completed at 3 sites in 2 countries. Open to female participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2017-09-11.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
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.
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.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 18 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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 · Drug: paclitaxel · Biological: trastuzumab · Procedure: therapeutic conventional surgery · Other: pharmacological study · Other: laboratory biomarker analysis
Given PO
Also known as: GSK572016, GW-572016, GW2016, Lapatinib, Tykerb
Given IV
Also known as: Anzatax, Asotax, TAX, Taxol
Given IV
Also known as: anti-c-erB-2, Herceptin, MOAB HER2
Undergo lumpectomy or mastectomy
Correlative studies
Also known as: pharmacological studies
Correlative studies
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 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.
Time frame: From baseline to 18 weeks
Number of Participants With Pathological Complete Response (pCR)
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.
Time frame: Up to 12 weeks
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
Cellular response will be documented and calculated for rate in all patients.
Time frame: Up to 18 weeks
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
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."
Time frame: From baseline to 24 weeks
Number of Participants With Treatment-Related Toxicities
Time frame: Up to 12 weeks after completion of study treatment
| Milestone | Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery) |
|---|---|
| Started | 18 |
| Completed | 18 |
| Not completed | 0 |
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.
| Participants | Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery) |
|---|---|
| baseline CD44v expression : pCR | 5 |
| baseline CD44v expression : non-pCR | 3 |
| CD44v expression at 6 weeks : pCR | 0 |
| CD44v expression at 6 weeks : non-pCR | 4 |
| CD44v expression at 18 weeks : pCR | 0 |
| CD44v expression at 18 weeks : non-pCR | 5 |
| baseline ALDH1 expression : pCR | 8 |
| baseline ALDH1 expression : non-pCR | 10 |
| ALDH1 expression at 6 weeks : pCR | 7 |
| ALDH1 expression at 6 weeks : non-pCR | 10 |
| ALDH1 expression at 18 weeks : pCR | 8 |
| ALDH1 expression at 18 weeks : non-pCR | 9 |
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.
| Participants | Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery) |
|---|---|
| Number of Participants With Pathological Complete Response (pCR) | 8 |
Cellular response will be documented and calculated for rate in all patients.
| participants | Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery) |
|---|---|
| positive cellular response at 6 weeks | 4 |
| positive cellular response at 18 weeks | 10 |
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."
No measurements were reported for this outcome.
| participants | Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery) |
|---|---|
| Grade 3 ALT increase | 2 |
| Grade 3 GGT increase | 1 |
| Grade 3 leukopenia | 1 |
| Grade 3 neutropenia | 1 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery) | 0/18 (0%) | 0/18 (0%) | 17/18 (94.4%) |
| Event | Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery) |
|---|---|
| diarrheaGastrointestinal disorders | 17/18 |
| oral mucositisGastrointestinal disorders | 14/18 |
| hand-foot syndromeSkin and subcutaneous tissue disorders | 13/18 |
| increased alanine aminotransferase levelInvestigations | 12/18 |
| increased aspartate aminotransferaseInvestigations | 11/18 |
| rashSkin and subcutaneous tissue disorders | 10/18 |
| Age, Categorical(Participants) | Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery) |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 18 |
| >=65 years | 0 |
| Sex: Female, Male(Participants) | Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery) |
|---|---|
| Female | 18 |
| Male | 0 |
| Region of Enrollment(participants) | Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery) |
|---|---|
| Japan | 18 |
This study is completed, as verified in Aug 2017. You cannot join it, but the record below documents what was studied.
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National Cancer Institute (NCI)