Trial Outcomes & Findings for Lapatinib Ditosylate, Trastuzumab, Paclitaxel, and Surgery in Treating Patients With Breast Cancer (NCT NCT01688609)
NCT ID: NCT01688609
Last Updated: 2017-09-11
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
18 participants
Primary outcome timeframe
From baseline to 18 weeks
Results posted on
2017-09-11
Participant Flow
Participant milestones
| Measure |
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.
lapatinib ditosylate: Given PO
paclitaxel: Given IV
trastuzumab: Given IV
therapeutic conventional surgery: Undergo lumpectomy or mastectomy
pharmacological study: Correlative studies
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Overall Study
STARTED
|
18
|
|
Overall Study
COMPLETED
|
18
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Lapatinib Ditosylate, Trastuzumab, Paclitaxel, and Surgery in Treating Patients With Breast Cancer
Baseline characteristics by cohort
| Measure |
Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery)
n=18 Participants
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.
lapatinib ditosylate: Given PO
paclitaxel: Given IV
trastuzumab: Given IV
therapeutic conventional surgery: Undergo lumpectomy or mastectomy
pharmacological study: Correlative studies
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
18 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
18 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From baseline to 18 weeksFor 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.
Outcome measures
| Measure |
Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery)
n=18 Participants
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.
lapatinib ditosylate: Given PO
paclitaxel: Given IV
trastuzumab: Given IV
therapeutic conventional surgery: Undergo lumpectomy or mastectomy
pharmacological study: Correlative studies
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks
baseline CD44v expression : pCR
|
5 Participants
|
|
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks
baseline CD44v expression : non-pCR
|
3 Participants
|
|
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks
CD44v expression at 6 weeks : pCR
|
0 Participants
|
|
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks
CD44v expression at 6 weeks : non-pCR
|
4 Participants
|
|
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks
CD44v expression at 18 weeks : pCR
|
0 Participants
|
|
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks
CD44v expression at 18 weeks : non-pCR
|
5 Participants
|
|
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks
baseline ALDH1 expression : pCR
|
8 Participants
|
|
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks
baseline ALDH1 expression : non-pCR
|
10 Participants
|
|
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks
ALDH1 expression at 6 weeks : pCR
|
7 Participants
|
|
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks
ALDH1 expression at 6 weeks : non-pCR
|
10 Participants
|
|
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks
ALDH1 expression at 18 weeks : pCR
|
8 Participants
|
|
Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks
ALDH1 expression at 18 weeks : non-pCR
|
9 Participants
|
PRIMARY outcome
Timeframe: Up to 12 weeksThe 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.
Outcome measures
| Measure |
Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery)
n=18 Participants
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.
lapatinib ditosylate: Given PO
paclitaxel: Given IV
trastuzumab: Given IV
therapeutic conventional surgery: Undergo lumpectomy or mastectomy
pharmacological study: Correlative studies
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Number of Participants With Pathological Complete Response (pCR)
|
8 Participants
|
SECONDARY outcome
Timeframe: Up to 18 weeksCellular response will be documented and calculated for rate in all patients.
Outcome measures
| Measure |
Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery)
n=18 Participants
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.
lapatinib ditosylate: Given PO
paclitaxel: Given IV
trastuzumab: Given IV
therapeutic conventional surgery: Undergo lumpectomy or mastectomy
pharmacological study: Correlative studies
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
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
positive cellular response at 6 weeks
|
4 participants
|
|
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
positive cellular response at 18 weeks
|
10 participants
|
SECONDARY outcome
Timeframe: From baseline to 24 weeksPopulation: The study was not able to determine the cut off value of total and phorylated RTK ratio. Assays were not reliable. Data of EGFR mutations were not collected.
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."
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 12 weeks after completion of study treatmentOutcome measures
| Measure |
Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery)
n=18 Participants
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.
lapatinib ditosylate: Given PO
paclitaxel: Given IV
trastuzumab: Given IV
therapeutic conventional surgery: Undergo lumpectomy or mastectomy
pharmacological study: Correlative studies
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Number of Participants With Treatment-Related Toxicities
Grade 3 ALT increase
|
2 participants
|
|
Number of Participants With Treatment-Related Toxicities
Grade 3 GGT increase
|
1 participants
|
|
Number of Participants With Treatment-Related Toxicities
Grade 3 leukopenia
|
1 participants
|
|
Number of Participants With Treatment-Related Toxicities
Grade 3 neutropenia
|
1 participants
|
Adverse Events
Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery)
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment (Lapatinib, Trastuzumab, Paclitaxel, Surgery)
n=18 participants at risk
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.
lapatinib ditosylate: Given PO
paclitaxel: Given IV
trastuzumab: Given IV
therapeutic conventional surgery: Undergo lumpectomy or mastectomy
pharmacological study: Correlative studies
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Gastrointestinal disorders
diarrhea
|
94.4%
17/18
|
|
Gastrointestinal disorders
oral mucositis
|
77.8%
14/18
|
|
Skin and subcutaneous tissue disorders
hand-foot syndrome
|
72.2%
13/18
|
|
Investigations
increased alanine aminotransferase level
|
66.7%
12/18
|
|
Investigations
increased aspartate aminotransferase
|
61.1%
11/18
|
|
Skin and subcutaneous tissue disorders
rash
|
55.6%
10/18
|
Additional Information
Dr. Teruo Yamauchi
St. Luke's International Hospital
Phone: +81-3-3541-5151
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60