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Trial record 20 of 99 for:    FEC

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

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ClinicalTrials.gov Identifier: NCT00524303
Recruitment Status : Completed
First Posted : September 3, 2007
Results First Posted : August 11, 2011
Last Update Posted : November 11, 2016
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasms, Breast
Interventions Drug: Trastuzumab
Drug: Paclitaxel
Drug: FEC75
Drug: Lapatinib
Enrollment 100
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Trastuzumab Lapatinib Trastuzumab+Lapatinib
Hide Arm/Group Description Participants received trastuzumab alone (a loading dose of 4 milligrams [mg]/kilogram [kg] on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter). Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil [5-FU] 500 mg/meters squared [m^2], epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab. Participants received lapatinib alone (1250 mg orally [PO] once daily [QD]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib. Participants received trastuzumab (given as in Arm 1) and lapatinib (750/1000 mg PO QD). Participants were treated with these medications in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab+lapatinib.
Period Title: Overall Study
Started 33 34 33
Completed 21 24 15
Not Completed 12 10 18
Reason Not Completed
Lost to Follow-up             6             0             3
Protocol Violation             0             1             1
Withdrawal by Subject             3             0             4
Death             0             2             3
Adverse Event             1             2             3
Did not Complete Study Dosing             1             0             0
Worsening Peripheral Neuropathy             1             0             0
Disease Progression             0             4             1
Disease Recurrence             0             1             0
Sponsor Request             0             0             1
Physician Decision             0             0             1
Completed 5 years             0             0             1
Arm/Group Title Trastuzumab Lapatinib Trastuzumab+Lapatinib Total
Hide Arm/Group Description Participants received trastuzumab alone (a loading dose of 4 milligrams [mg]/kilogram [kg] on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter). Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil [5-FU] 500 mg/meters squared [m^2], epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab. Participants received lapatinib alone (1250 mg orally [PO] once daily [QD]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib. Participants received trastuzumab (given as in Arm 1) and lapatinib (750/1000 mg PO QD). Participants were treated with these medications in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab+lapatinib. Total of all reporting groups
Overall Number of Baseline Participants 33 34 33 100
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 33 participants 34 participants 33 participants 100 participants
51.1  (10.90) 50.8  (8.76) 49.2  (10.47) 50.4  (10.01)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 34 participants 33 participants 100 participants
Female
33
 100.0%
34
 100.0%
33
 100.0%
100
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 34 participants 33 participants 100 participants
African American/African heritage 8 1 2 11
American Indian or Alaska native 0 0 1 1
Asian - Central/South Asian heritage 0 1 0 1
Asian - East Asian heritage 0 1 0 1
Asian - South East Asian heritage 0 2 1 3
White - Arabic/North African heritage 0 1 0 1
White - White/Caucasian/European heritage 25 27 29 81
Mixed race 0 1 0 1
1.Primary Outcome
Title Percentage of Participants With Overall Pathological Complete Response (pCR) After 26 Weeks of Therapy
Hide Description A pCR in the breast was defined as no pathologic evidence of invasive disease (residual ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS] was allowed). A pCR in the axillary lymph node(s) was defined as no evidence of breast cancer cells in the lymph node (including subcapsular sinus). Overall pCR was defined as the sum of pCR in the breast and pCR in the lymph nodes. 26 weeks of therapy comprised the 2-week run-in phase, 12 weeks of treatment with FEC, and 12 weeks of treatment with Paclitaxel.
Time Frame Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat-Evaluable (ITT-E) Population: ITT participants with evaluable tumor responses who had been >=75% compliant to 5-fluorouracil (5-FU) 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 (FEC75) and paclitaxel 80 mg/m^2 and had undergone surgery.
Arm/Group Title Trastuzumab Lapatinib Trastuzumab+Lapatinib
Hide Arm/Group Description:
Participants received trastuzumab alone (a loading dose of 4 milligrams [mg]/kilogram [kg] on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter). Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil [5-FU] 500 mg/meters squared [m^2], epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab.
Participants received lapatinib alone (1250 mg orally [PO] once daily [QD]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib.
Participants received trastuzumab (given as in Arm 1) and lapatinib (750/1000 mg PO QD). Participants were treated with these medications in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab+lapatinib.
Overall Number of Participants Analyzed 26 29 23
Measure Type: Number
Unit of Measure: percentage of participants
54.0 45.0 74.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab, Lapatinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent difference
Estimated Value -9
Confidence Interval (2-Sided) 95%
-38.1 to 17.9
Estimation Comments Approximate 95% confidence interval for the difference in response rates between the trastuzumab arm and the lapatinib arm was calculated.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Trastuzumab, Trastuzumab+Lapatinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent difference
Estimated Value 20
Confidence Interval (2-Sided) 95%
-8.0 to 49.4
Estimation Comments Approximate 95% confidence interval for the difference in response rates between the transtuzumab arm and the transtuzumab + lapatinib arm was calculated.
2.Secondary Outcome
Title Percentage of Participants With Clinical Complete Response (cCR) at 26 Weeks or at End of Treatment (EOT) or Early Withdrawal
Hide Description cCR was defined as the percentage of participants achieving either a Complete Response (CR) or a Partial Response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Time Frame Week 26 or EOT or Early withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: all randomized participants regardless of whether they had received any treatment.
Arm/Group Title Trastuzumab Lapatinib Trastuzumab+Lapatinib
Hide Arm/Group Description:
Participants received trastuzumab alone (a loading dose of 4 milligrams [mg]/kilogram [kg] on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter). Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil [5-FU] 500 mg/meters squared [m^2], epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab.
Participants received lapatinib alone (1250 mg orally [PO] once daily [QD]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib.
Participants received trastuzumab (given as in Arm 1) and lapatinib (750/1000 mg PO QD). Participants were treated with these medications in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab+lapatinib.
Overall Number of Participants Analyzed 33 34 33
Measure Type: Number
Unit of Measure: percentage of participants
61.0 68.0 61.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab, Lapatinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.627
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Difference
Estimated Value 7
Confidence Interval (2-Sided) 95%
-17.8 to 32.5
Estimation Comments Approximate 95% confidence interval for the difference in response rates between the transtuzumab arm and the lapatinib arm was calculated.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Trastuzumab, Trastuzumab+Lapatinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Difference
Estimated Value 0
Confidence Interval (2-Sided) 95%
-25.1 to 25.1
Estimation Comments Approximate 95% confidence interval for the difference in response rates between the transtuzumab arm and the transtuzumab + lapatinib arm was calculated.
3.Secondary Outcome
Title Percentage of Participants (Par.) With Disease-free Survival (DFS) at the End of 5 Years From Randomization
Hide Description Percentage is the Kaplan Meier estimate of DFS. DFS is time from randomization until disease recurrence (contralateral breast cancer; second primary cancer; progression during neo-adjuvant treatment; or death from any cause). Par. who experienced progression during treatment and were withdrawn were considered to have a DFS event at withdrawal.
Time Frame From first dose date until disease progression, assessed up to a maximum of 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Trastuzumab Lapatinib Trastuzumab+Lapatinib
Hide Arm/Group Description:
Participants received trastuzumab alone (a loading dose of 4 milligrams [mg]/kilogram [kg] on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter). Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil [5-FU] 500 mg/meters squared [m^2], epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab.
Participants received lapatinib alone (1250 mg orally [PO] once daily [QD]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib.
Participants received trastuzumab (given as in Arm 1) and lapatinib (750/1000 mg PO QD). Participants were treated with these medications in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab+lapatinib.
Overall Number of Participants Analyzed 33 34 33
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
90
(72 to 97)
67
(47 to 80)
66
(44 to 82)
4.Secondary Outcome
Title Number of Participants With the Indicated Electrocardiogram (ECG) Status at Baseline and at EOT or Early Withdrawal
Hide Description 12-lead ECGs were performed, and participants were classified as having normal ECG, abnormal- not clinically significant (NCS) ECG, and abnormal-clinically significant (CS) ECG per investigator opinion and reported result.
Time Frame Baseline and EOT (up to Week 26) or Early withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all randomized participants (par) who received at least one dose of investigational product, based on actual treatment received if this differed from that to which par was randomized. Not all par were analyzed: some par were randomized to an arm they did not want or par were randomized in error (eligibility criteria weren’t met).
Arm/Group Title Trastuzumab Lapatinib Trastuzumab+Lapatinib
Hide Arm/Group Description:
Participants received trastuzumab alone (a loading dose of 4 milligrams [mg]/kilogram [kg] on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter). Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil [5-FU] 500 mg/meters squared [m^2], epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab.
Participants received lapatinib alone (1250 mg orally [PO] once daily [QD]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib.
Participants received trastuzumab (given as in Arm 1) and lapatinib (750/1000 mg PO QD). Participants were treated with these medications in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab+lapatinib.
Overall Number of Participants Analyzed 28 32 30
Measure Type: Number
Unit of Measure: participants
Baseline, Normal, n= 28, 32, 30 18 23 23
Baseline, Abnormal-NCS, n= 28, 32, 30 10 8 7
Baseline, Abnormal-CS, n= 28, 32, 30 0 1 0
EOT/early withdrawal, Normal, n= 16, 21, 16 10 12 12
EOT/early withdrawal, Abnormal-NCS, n= 16, 21, 16 6 8 4
EOT/early withdrawal, Abnormal-CS, n= 16, 21, 16 0 1 0
5.Secondary Outcome
Title Cumulative Number of Participants With at Least One Decrease of More Than or Equal to 20% in Left Ventricular Ejection Fraction (LVEF) at the Indicated Time Points Compared to LVEF at Baseline
Hide Description LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction and is used to determine cardiac function. LVEF was measured by performing echocardiogram (ECHO). If ECHO could not be performed or if the investigator believed that it was not conclusive to evaluate LVEF, then a multigated acquisition (MUGA) scan was performed.
Time Frame Weeks 3, 9, and 15; EOT or early withdrawal; and 3- and 6-month survival follow-up after last chemotherapy course
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Not all participants in the Safety Population were analyzed: some participants were randomized to an arm they did not want or participants were randomized in error (eligibility criteria weren’t met).
Arm/Group Title Trastuzumab Lapatinib Trastuzumab+Lapatinib
Hide Arm/Group Description:
Participants received trastuzumab alone (a loading dose of 4 milligrams (mg)/kilogram (kg) on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter. Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil [5-FU] 500 mg/meters squared [m^2], epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel 80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab.
Participants received lapatinib alone (1250 mg orally [PO] once daily [QD]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel 80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib.
Participants received trastuzumab (given as in Arm 1) and lapatinib (750/1000 mg PO QD). Participants were treated with these medications in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel 80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab+lapatinib.
Overall Number of Participants Analyzed 32 34 31
Measure Type: Number
Unit of Measure: participants
Week 3, n= 30, 31, 26 1 0 1
Week 9, n= 30, 32, 27 1 0 1
Week 15, n= 31, 34, 28 1 2 2
Early withdrawal/EOT, n= 31, 34, 28 1 4 2
3-month survival follow-up, n= 31, 34, 28 2 4 3
6-month survival follow-up, n= 31, 34, 28 4 4 4
6.Other Pre-specified Outcome
Title Mean Intra-tumoral Expression of the Indicated Proteins at Baseline and Day 14
Hide Description Expression (exp) of biomarker proteins (prot) were analyzed to determine if individual prot levels either in the Baseline or Day 14 breast tumor biopsy specimen correlated with breast pCR. A biomarker indicates a change in exp or state of a prot that correlates with the risk or disease progression, or with the susceptibility of the disease to a given treatment. Biomarkers are characteristic biological properties that can be detected and measured in parts of the body like blood or tissue. pCR=yes: participants (par.) had breast pCR. pCR=no: par. did not have breast pCR. Prot exp values are represented as normalized, scaled values; the unit of measurement is unit-less. Raw exp values were processed as follows: background subtraction of the raw exp value, then that value divided by beta-acting exp to normalize the exp value. A Standard Z score was calculated to scale the exp value.
Time Frame Tumor core biopsy taken at Baseline and Treatment Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Only those participants with matched pairs of biopsy samples for analysis at Baseline and on Day 14 were analyzed.
Arm/Group Title Trastuzumab Lapatinib
Hide Arm/Group Description:
Participants received trastuzumab alone (a loading dose of 4 milligrams [mg]/kilogram [kg] on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter). Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil [5-FU] 500 mg/meters squared [m^2], epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab.
Participants received lapatinib alone (1250 mg orally [PO] once daily [QD]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib.
Overall Number of Participants Analyzed 11 9
Mean (Standard Deviation)
Unit of Measure: : normalized relative expression level
Baseline, EGFR_Tyr1068; pCR=yes, n=0, 4 NA [1]   (NA) -0.70  (0.47)
Baseline, Baseline, EGFR_Tyr1068; pCR=no, n=0, 11 NA [1]   (NA) 0.05  (0.55)
Post Baseline, EGFR_Tyr1068; pCR=yes, n=9, 0 0.65  (1.02) NA [1]   (NA)
Post Baseline, EGFR_Tyr1068; pCR=no, n=6, 0 -0.26  (0.56) NA [1]   (NA)
Day 14, pSTAT5; pCR=yes, n=11, 6 NA [1]   (NA) NA [1]   (NA)
Day 14, pSTAT5; pCR=no, n=9, 11 NA [1]   (NA) NA [1]   (NA)
Post Baseline, PI3K; pCR=yes, n=0, 5 NA [1]   (NA) 0.46  (0.73)
Post Baseline, PI3K; pCR=no, n=0, 10 NA [1]   (NA) -0.53  (0.67)
Post Baseline, LC3B; pCR=yes, n=0, 5 NA [1]   (NA) 0.68  (0.81)
Post Baseline, LC3B; pCR=no, n=0, 10 NA [1]   (NA) -0.43  (0.75)
Post Baseline, MMP9; pCR=yes, n=0, 5 NA [1]   (NA) 0.71  (0.34)
Post Baseline, MMP9; pCR=no, n=0, 5 NA [1]   (NA) -0.48  (0.48)
Post Baseline, GSK3_a_b_Tyr279_216; pCR=yes, n=8,0 0.26  (0.82) NA [1]   (NA)
Post Baseline, GSK3_a_b_Tyr279_216; pCR=no, n=5,0 -0.86  (0.67) NA [1]   (NA)
[1]
This protein was not significantly expressed at this time point in this treatment arm.
7.Other Pre-specified Outcome
Title Cancer Stem Cells and the Correlation to Response/Non-response to Treatment
Hide Description Stem cell data were of poor quality and thus could not be analyzed. Increases or decreases in cancer stem cells and how the changes correlated with response/non-response to treatment were to have been assessed.
Time Frame Tumor core biopsy taken at Baseline and Treatment Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Trastuzumab Lapatinib Trastuzumab+Lapatinib
Hide Arm/Group Description:
Participants received trastuzumab alone (a loading dose of 4 milligrams [mg]/kilogram [kg] on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter). Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil [5-FU] 500 mg/meters squared [m^2], epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab.
Participants received lapatinib alone (1250 mg orally [PO] once daily [QD]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib.
Participants received trastuzumab (given as in Arm 1) and lapatinib (750/1000 mg PO QD). Participants were treated with these medications in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab+lapatinib.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Other Pre-specified Outcome
Title Transcriptional Profiling of Total RNA and the Correlation to Response/Non-response to Treatment
Hide Description Transcriptional data were of poor quality and thus could not be analyzed. Gene pathways that correlate with response/non-response to treatment were to have been evaluated. The unit of measure is unit less; however, the processed values would be considered normalized relative expression level.
Time Frame Tumor core biopsy taken at Baseline and Treatment Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Trastuzumab Lapatinib Trastuzumab+Lapatinib
Hide Arm/Group Description:
Participants received trastuzumab alone (a loading dose of 4 milligrams [mg]/kilogram [kg] on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter). Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil [5-FU] 500 mg/meters squared [m^2], epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab.
Participants received lapatinib alone (1250 mg orally [PO] once daily [QD]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib.
Participants received trastuzumab (given as in Arm 1) and lapatinib (750/1000 mg PO QD). Participants were treated with these medications in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab+lapatinib.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description In the Safety Population, serious and non-serious adverse events were collected from all randomized participants who received at least one dose of investigational product and was based on the actual treatment received if this differed from that to which the participant was randomized.
 
Arm/Group Title Trastuzumab Lapatinib Trastuzumab+Lapatinib
Hide Arm/Group Description Participants received trastuzumab alone (a loading dose of 4 milligrams [mg]/kilogram [kg] on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter). Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil [5-FU] 500 mg/meters squared [m^2], epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab. Participants received lapatinib alone (1250 mg orally [PO] once daily [QD]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib. Participants received trastuzumab (given as in Arm 1) and lapatinib (750/1000 mg PO QD). Participants were treated with these medications in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab+lapatinib.
All-Cause Mortality
Trastuzumab Lapatinib Trastuzumab+Lapatinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Trastuzumab Lapatinib Trastuzumab+Lapatinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/32 (21.88%)   7/34 (20.59%)   8/31 (25.81%) 
Blood and lymphatic system disorders       
Febrile nuetropenia  1  3/32 (9.38%)  0/34 (0.00%)  2/31 (6.45%) 
Neutropenia  1  3/32 (9.38%)  0/34 (0.00%)  1/31 (3.23%) 
Anaemia  1  1/32 (3.13%)  0/34 (0.00%)  0/31 (0.00%) 
Gastrointestinal disorders       
Diarrhoea  1  0/32 (0.00%)  2/34 (5.88%)  2/31 (6.45%) 
Vomiting  1  0/32 (0.00%)  1/34 (2.94%)  1/31 (3.23%) 
Nausea  1  0/32 (0.00%)  0/34 (0.00%)  1/31 (3.23%) 
Stomatitis  1  0/32 (0.00%)  0/34 (0.00%)  1/31 (3.23%) 
General disorders       
Pyrexia  1  0/32 (0.00%)  3/34 (8.82%)  0/31 (0.00%) 
Chest discomfort  1  0/32 (0.00%)  0/34 (0.00%)  1/31 (3.23%) 
Infections and infestations       
Cellilitis  1  0/32 (0.00%)  1/34 (2.94%)  0/31 (0.00%) 
Diverticulitis  1  0/32 (0.00%)  1/34 (2.94%)  0/31 (0.00%) 
Gastroenteritis  1  0/32 (0.00%)  0/34 (0.00%)  1/31 (3.23%) 
Upper respiratory tract infection  1  1/32 (3.13%)  0/34 (0.00%)  0/31 (0.00%) 
Urinary tract infection  1  0/32 (0.00%)  0/34 (0.00%)  1/31 (3.23%) 
Investigations       
Liver function test abnormal  1  0/32 (0.00%)  0/34 (0.00%)  1/31 (3.23%) 
Metabolism and nutrition disorders       
Dehydration  1  0/32 (0.00%)  1/34 (2.94%)  1/31 (3.23%) 
Hyponatraemia  1  0/32 (0.00%)  1/34 (2.94%)  0/31 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism  1  3/32 (9.38%)  0/34 (0.00%)  1/31 (3.23%) 
Dysponea  1  0/32 (0.00%)  0/34 (0.00%)  1/31 (3.23%) 
Skin and subcutaneous tissue disorders       
Swelling face  1  0/32 (0.00%)  1/34 (2.94%)  0/31 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  0/32 (0.00%)  0/34 (0.00%)  1/31 (3.23%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA, Version 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Trastuzumab Lapatinib Trastuzumab+Lapatinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   31/32 (96.88%)   34/34 (100.00%)   31/31 (100.00%) 
Blood and lymphatic system disorders       
Neutropenia  1  13/32 (40.63%)  12/34 (35.29%)  15/31 (48.39%) 
Anemia  1  10/32 (31.25%)  12/34 (35.29%)  12/31 (38.71%) 
Leukopenia  1  3/32 (9.38%)  4/34 (11.76%)  5/31 (16.13%) 
Thrombocytopenia  1  1/32 (3.13%)  4/34 (11.76%)  3/31 (9.68%) 
Febrile neutropenia  1  0/32 (0.00%)  2/34 (5.88%)  2/31 (6.45%) 
Cardiac disorders       
Tachycardia  1  2/32 (6.25%)  1/34 (2.94%)  1/31 (3.23%) 
Palpitations  1  1/32 (3.13%)  2/34 (5.88%)  0/31 (0.00%) 
Eye disorders       
Lacrimation increased  1  3/32 (9.38%)  0/34 (0.00%)  2/31 (6.45%) 
Vision blurred  1  1/32 (3.13%)  2/34 (5.88%)  2/31 (6.45%) 
Eye irritation  1  0/32 (0.00%)  2/34 (5.88%)  0/31 (0.00%) 
Visual impairment  1  0/32 (0.00%)  0/34 (0.00%)  2/31 (6.45%) 
Gastrointestinal disorders       
Nausea  1  26/32 (81.25%)  26/34 (76.47%)  26/31 (83.87%) 
Diarrhoea  1  17/32 (53.13%)  29/34 (85.29%)  31/31 (100.00%) 
Vomiting  1  7/32 (21.88%)  15/34 (44.12%)  8/31 (25.81%) 
Constipation  1  12/32 (37.50%)  8/34 (23.53%)  6/31 (19.35%) 
Stomatitis  1  5/32 (15.63%)  7/34 (20.59%)  7/31 (22.58%) 
Dyspepsia  1  6/32 (18.75%)  5/34 (14.71%)  7/31 (22.58%) 
Abdominal pain  1  5/32 (15.63%)  6/34 (17.65%)  3/31 (9.68%) 
Gastrooesophageal reflux disease  1  4/32 (12.50%)  3/34 (8.82%)  5/31 (16.13%) 
Haemorrhoids  1  1/32 (3.13%)  3/34 (8.82%)  2/31 (6.45%) 
Oral pain  1  1/32 (3.13%)  1/34 (2.94%)  4/31 (12.90%) 
Abdominal pain upper  1  1/32 (3.13%)  1/34 (2.94%)  3/31 (9.68%) 
Dry mouth  1  1/32 (3.13%)  3/34 (8.82%)  1/31 (3.23%) 
Abdominal distension  1  1/32 (3.13%)  3/34 (8.82%)  0/31 (0.00%) 
Haemorrhoidal haemorrhage  1  2/32 (6.25%)  0/34 (0.00%)  1/31 (3.23%) 
Mouth ulceration  1  1/32 (3.13%)  2/34 (5.88%)  0/31 (0.00%) 
Proctalgia  1  0/32 (0.00%)  0/34 (0.00%)  2/31 (6.45%) 
General disorders       
Fatigue  1  22/32 (68.75%)  24/34 (70.59%)  24/31 (77.42%) 
Oedema peripheral  1  5/32 (15.63%)  10/34 (29.41%)  7/31 (22.58%) 
Mucosal inflammation  1  6/32 (18.75%)  7/34 (20.59%)  8/31 (25.81%) 
Pyrexia  1  3/32 (9.38%)  6/34 (17.65%)  9/31 (29.03%) 
Pain  1  3/32 (9.38%)  5/34 (14.71%)  5/31 (16.13%) 
Asthenia  1  4/32 (12.50%)  2/34 (5.88%)  3/31 (9.68%) 
Catheter site pain  1  5/32 (15.63%)  0/34 (0.00%)  2/31 (6.45%) 
Chills  1  5/32 (15.63%)  0/34 (0.00%)  1/31 (3.23%) 
Non-cardiac chest pain  1  1/32 (3.13%)  4/34 (11.76%)  0/31 (0.00%) 
Chest discomfort  1  2/32 (6.25%)  2/34 (5.88%)  0/31 (0.00%) 
Axillary pain  1  0/32 (0.00%)  0/34 (0.00%)  2/31 (6.45%) 
Catheter site related reaction  1  0/32 (0.00%)  2/34 (5.88%)  0/31 (0.00%) 
Face oedema  1  0/32 (0.00%)  2/34 (5.88%)  0/31 (0.00%) 
Immune system disorders       
Seasonal allergy  1  1/32 (3.13%)  2/34 (5.88%)  1/31 (3.23%) 
Infections and infestations       
Urinary tract infection  1  4/32 (12.50%)  5/34 (14.71%)  5/31 (16.13%) 
Upper respiratory tract infection  1  5/32 (15.63%)  4/34 (11.76%)  4/31 (12.90%) 
Rhinitis  1  2/32 (6.25%)  3/34 (8.82%)  1/31 (3.23%) 
Nasopharyngitis  1  3/32 (9.38%)  2/34 (5.88%)  0/31 (0.00%) 
Sinusitis  1  1/32 (3.13%)  2/34 (5.88%)  2/31 (6.45%) 
Vulvovaginal mycotic infection  1  2/32 (6.25%)  0/34 (0.00%)  3/31 (9.68%) 
Herpes zoster  1  1/32 (3.13%)  1/34 (2.94%)  2/31 (6.45%) 
Localised infection  1  0/32 (0.00%)  2/34 (5.88%)  2/31 (6.45%) 
Candidiasis  1  2/32 (6.25%)  1/34 (2.94%)  0/31 (0.00%) 
Cellulitis  1  0/32 (0.00%)  2/34 (5.88%)  1/31 (3.23%) 
Oral herpes  1  0/32 (0.00%)  2/34 (5.88%)  1/31 (3.23%) 
Gastroenteritis viral  1  0/32 (0.00%)  2/34 (5.88%)  0/31 (0.00%) 
Injury, poisoning and procedural complications       
Procedural pain  1  0/32 (0.00%)  0/34 (0.00%)  2/31 (6.45%) 
Investigations       
Haemoglobin decreased  1  1/32 (3.13%)  6/34 (17.65%)  4/31 (12.90%) 
Neutrophil count decreased  1  2/32 (6.25%)  4/34 (11.76%)  3/31 (9.68%) 
Alanine aminotransferase increased  1  1/32 (3.13%)  3/34 (8.82%)  4/31 (12.90%) 
Aspartate aminotransferase increased  1  1/32 (3.13%)  3/34 (8.82%)  4/31 (12.90%) 
Weight decreased  1  0/32 (0.00%)  3/34 (8.82%)  5/31 (16.13%) 
Platelet count decreased  1  1/32 (3.13%)  2/34 (5.88%)  2/31 (6.45%) 
Blood lactate dehygrogenase increased  1  1/32 (3.13%)  1/34 (2.94%)  2/31 (6.45%) 
White blood cell count decreased  1  1/32 (3.13%)  3/34 (8.82%)  0/31 (0.00%) 
Body temperature increased  1  3/32 (9.38%)  0/34 (0.00%)  0/31 (0.00%) 
Alanine aminotranferase decreased  1  0/32 (0.00%)  2/34 (5.88%)  0/31 (0.00%) 
Metabolism and nutrition disorders       
Hypokalaemia  1  2/32 (6.25%)  10/34 (29.41%)  11/31 (35.48%) 
Decreased appetite  1  5/32 (15.63%)  7/34 (20.59%)  7/31 (22.58%) 
Dehydration  1  0/32 (0.00%)  2/34 (5.88%)  5/31 (16.13%) 
Hypocalcaemia  1  0/32 (0.00%)  2/34 (5.88%)  0/31 (0.00%) 
Musculoskeletal and connective tissue disorders       
Myalgia  1  4/32 (12.50%)  10/34 (29.41%)  9/31 (29.03%) 
Arthralgia  1  5/32 (15.63%)  11/34 (32.35%)  6/31 (19.35%) 
Back pain  1  6/32 (18.75%)  3/34 (8.82%)  5/31 (16.13%) 
Pain in extremity  1  6/32 (18.75%)  3/34 (8.82%)  5/31 (16.13%) 
Muscle spasms  1  4/32 (12.50%)  3/34 (8.82%)  3/31 (9.68%) 
Muscular weakness  1  0/32 (0.00%)  4/34 (11.76%)  3/31 (9.68%) 
Bone pain  1  1/32 (3.13%)  3/34 (8.82%)  2/31 (6.45%) 
Musculoskeletal pain  1  0/32 (0.00%)  1/34 (2.94%)  2/31 (6.45%) 
Neck pain  1  0/32 (0.00%)  3/34 (8.82%)  0/31 (0.00%) 
Nervous system disorders       
Neuropathy peripheral  1  15/32 (46.88%)  19/34 (55.88%)  14/31 (45.16%) 
Dysgeusia  1  4/32 (12.50%)  10/34 (29.41%)  9/31 (29.03%) 
Headache  1  8/32 (25.00%)  6/34 (17.65%)  7/31 (22.58%) 
Dizziness  1  3/32 (9.38%)  5/34 (14.71%)  2/31 (6.45%) 
Peripheral sensory neuropathy  1  1/32 (3.13%)  3/34 (8.82%)  3/31 (9.68%) 
Syncope  1  1/32 (3.13%)  3/34 (8.82%)  2/31 (6.45%) 
Hypoaesthesia  1  0/32 (0.00%)  3/34 (8.82%)  2/31 (6.45%) 
Memory impairment  1  1/32 (3.13%)  2/34 (5.88%)  1/31 (3.23%) 
Tremor  1  1/32 (3.13%)  2/34 (5.88%)  0/31 (0.00%) 
Psychiatric disorders       
Insomnia  1  5/32 (15.63%)  6/34 (17.65%)  5/31 (16.13%) 
Anxiety  1  4/32 (12.50%)  5/34 (14.71%)  5/31 (16.13%) 
Depression  1  5/32 (15.63%)  5/34 (14.71%)  1/31 (3.23%) 
Renal and urinary disorders       
Dysuria  1  4/32 (12.50%)  3/34 (8.82%)  1/31 (3.23%) 
Reproductive system and breast disorders       
Breast pain  1  1/32 (3.13%)  3/34 (8.82%)  4/31 (12.90%) 
Vaginal haemorrhage  1  2/32 (6.25%)  0/34 (0.00%)  1/31 (3.23%) 
Respiratory, thoracic and mediastinal disorders       
Epistaxis  1  7/32 (21.88%)  10/34 (29.41%)  10/31 (32.26%) 
Cough  1  8/32 (25.00%)  3/34 (8.82%)  7/31 (22.58%) 
Dyspnoea  1  4/32 (12.50%)  6/34 (17.65%)  7/31 (22.58%) 
Oropharyngeal pain  1  6/32 (18.75%)  2/34 (5.88%)  6/31 (19.35%) 
Rhinorrhoea  1  5/32 (15.63%)  1/34 (2.94%)  2/31 (6.45%) 
Nasal congestion  1  3/32 (9.38%)  1/34 (2.94%)  2/31 (6.45%) 
Sinus congestion  1  2/32 (6.25%)  2/34 (5.88%)  1/31 (3.23%) 
Nasal ulcer  1  3/32 (9.38%)  0/34 (0.00%)  1/31 (3.23%) 
Dysphonia  1  0/32 (0.00%)  0/34 (0.00%)  2/31 (6.45%) 
Dysponoea exertional  1  0/32 (0.00%)  2/34 (5.88%)  0/31 (0.00%) 
Respiratory tract congestion  1  2/32 (6.25%)  0/34 (0.00%)  0/31 (0.00%) 
Rhinitis allergic  1  2/32 (6.25%)  0/34 (0.00%)  0/31 (0.00%) 
Skin and subcutaneous tissue disorders       
Rash  1  14/32 (43.75%)  28/34 (82.35%)  26/31 (83.87%) 
Alopecia  1  21/32 (65.63%)  24/34 (70.59%)  18/31 (58.06%) 
Nail disorder  1  4/32 (12.50%)  10/34 (29.41%)  8/31 (25.81%) 
Pruritus  1  3/32 (9.38%)  7/34 (20.59%)  6/31 (19.35%) 
Dry skin  1  3/32 (9.38%)  2/34 (5.88%)  4/31 (12.90%) 
Pruritus genralised  1  2/32 (6.25%)  3/34 (8.82%)  1/31 (3.23%) 
Night sweats  1  2/32 (6.25%)  1/34 (2.94%)  1/31 (3.23%) 
Skin hyperpigmentation  1  2/32 (6.25%)  0/34 (0.00%)  2/31 (6.45%) 
Pain of skin  1  1/32 (3.13%)  2/34 (5.88%)  0/31 (0.00%) 
Skin discolouration  1  2/32 (6.25%)  0/34 (0.00%)  1/31 (3.23%) 
Skin exfoliation  1  2/32 (6.25%)  0/34 (0.00%)  0/31 (0.00%) 
Vascular disorders       
Hot flush  1  4/32 (12.50%)  1/34 (2.94%)  3/31 (9.68%) 
Hypertension  1  1/32 (3.13%)  1/34 (2.94%)  3/31 (9.68%) 
Hypotension  1  1/32 (3.13%)  2/34 (5.88%)  0/31 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA, Version 14.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00524303     History of Changes
Other Study ID Numbers: LPT109096
First Submitted: August 31, 2007
First Posted: September 3, 2007
Results First Submitted: July 14, 2011
Results First Posted: August 11, 2011
Last Update Posted: November 11, 2016