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Lapatinib Combined With Paclitaxel For Patients With First-Line ErbB2-Amplified Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT00356811
Recruitment Status : Completed
First Posted : July 26, 2006
Results First Posted : July 21, 2014
Last Update Posted : July 21, 2014
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasms, Breast
Interventions Drug: Lapatinib oral tablets
Drug: Paclitaxel infusion
Enrollment 57
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Lapatinib With Paclitaxel
Hide Arm/Group Description Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel, administered as a 1-hour intravenous (IV) infusion at a dose of 80 mg/meters squared (m^2) on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Period Title: Overall Study
Started 57
Completed 8
Not Completed 49
Reason Not Completed
Death             35
Lost to Follow-up             2
Withdrawal by Subject             6
Participant Could Not Make a Checkup             1
Study Is Terminating             3
Site Closed during Follow-up             2
Arm/Group Title Lapatinib Plus Paclitaxel
Hide Arm/Group Description Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Baseline Participants 57
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 57 participants
52.3  (9.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants
Female
57
 100.0%
Male
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
White - White/Caucasian/European Heritage Number Analyzed 57 participants
57
1.Primary Outcome
Title Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC)
Hide Description OR is defined as the number of participants achieving either a CR or PR, per Response Evaulation Criteria in Solid Tumors (RECIST). The best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made >=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.
Time Frame From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants who received study medication.
Arm/Group Title Lapatinib Plus Paclitaxel
Hide Arm/Group Description:
Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 57
Measure Type: Number
Unit of Measure: Participants
CR 0
PR 29
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lapatinib Plus Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of participants
Estimated Value 50.9
Confidence Interval (2-Sided) 95%
37.3 to 64.4
Estimation Comments The estimated value represents the percentage of participants with a confirmed CR or PR.
2.Secondary Outcome
Title Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Investigator
Hide Description OR is defined as the number of participants achieving either a CR or PR, per RECIST. The best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the Investigator. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made >=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.
Time Frame From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib Plus Paclitaxel
Hide Arm/Group Description:
Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 57
Measure Type: Number
Unit of Measure: Participants
CR 3
PR 41
3.Secondary Outcome
Title Duration of Response (DoR), as Assessed by the IRC
Hide Description DoR is defined for the subset of participants who had a confirmed CR (disappearance of all TLs and non-TLs) or PR (>=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL[s]) as the time from the first documented evidence of a CR or PR until the first documentation of radiological PD or death due to breast cancer, if sooner. PD is defined as a >=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. For participants who did not progress or die, DoR was censored on the date of the last radiological scan. If a participant had only a Baseline visit or did not have a date of a radiological scan that was later than the date of initiation of anti-cancer therapy, DoR was censored at the start date of treatment.
Time Frame From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Week 86)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with CR or PR were analyzed.
Arm/Group Title Overall Study Arm
Hide Arm/Group Description:
Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 29
Median (95% Confidence Interval)
Unit of Measure: weeks
39.7
(26.9 to 50.0)
4.Secondary Outcome
Title Duration of Response (DoR), as Assessed by the Investigator
Hide Description DoR is defined for the subset of participants who had a confirmed CR (disappearance of all TLs and non-TLs) or PR (>=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL[s]) as the time from the first documented evidence of a CR or PR until the first documentation of radiological PD or death due to breast cancer, if sooner. PD is defined as a >=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. For participants who did not progress or die, DoR was censored on the date of the last radiological scan. If a participant had only a Baseline visit or did not have a date of a radiological scan that was later than the date of initiation of anti-cancer therapy, DoR was censored at the start date of treatment.
Time Frame From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Week 86)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with CR or PR were analyzed.
Arm/Group Title Lapatinib Plus Paclitaxel
Hide Arm/Group Description:
Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 44
Median (95% Confidence Interval)
Unit of Measure: Weeks
42.3
(37.7 to 64.1)
5.Secondary Outcome
Title Time to Response, as Assessed by the IRC
Hide Description Time to response is defined as the time from randomization until the first documented evidence of a PR or CR (whichever status is recorded first). Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the time to response taken as the first time the response was observed, not the confirmation assessment. Participants who withdraw with no tumor response were censored at the date of withdrawal from the study. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s). PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs.
Time Frame From randomization until the first documented evidence of a PR or CR (up to Week 86)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with CR or PR were analyzed.
Arm/Group Title Lapatinib Plus Paclitaxel
Hide Arm/Group Description:
Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 29
Median (95% Confidence Interval)
Unit of Measure: weeks
8.4
(7.9 to 11.1)
6.Secondary Outcome
Title Time to Response, as Assessed by the Investigator
Hide Description Time to response is defined as the time from randomization until the first documented evidence of a PR or CR (whichever status is recorded first). Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the time to response taken as the first time the response was observed, not the confirmation assessment. Participants who withdraw with no tumor response were censored at the date of withdrawal from the study. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s). PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs.
Time Frame From randomization until the first documented evidence of a PR or CR (up to Week 86)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with CR or PR were analyzed.
Arm/Group Title Lapatinib Plus Paclitaxel
Hide Arm/Group Description:
Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 44
Median (95% Confidence Interval)
Unit of Measure: Weeks
8.0
(7.9 to 8.1)
7.Secondary Outcome
Title Time to Progression, as Assessed by the IRC and the Investigator
Hide Description Time to progression is defined as the interval between the start date of treatment and the date of radiological disease progression or death due to breast cancer, whichever occurs first. Participents who did not progress or die were censored on the date of their last radiological assessment preceding the start of any additional anti-cancer therapy. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at a subsequent assessment made no less than 28 days after the original response.
Time Frame From the start date of treatment until the date of radiological disease progression or the date of death due to breast cancer (up to Week 86)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib Plus Paclitaxel
Hide Arm/Group Description:
Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 57
Median (95% Confidence Interval)
Unit of Measure: weeks
IRC
47.9 [1] 
(40.0 to NA)
Investigator
50.9
(47.0 to 64.3)
[1]
The upper limit of the 95% confidence interval could not be determined (not reached) because there were not enough events to be able to calculate it.
8.Secondary Outcome
Title Progression-free Survival, as Assessed by the IRC and the Investigator
Hide Description Progression-free survival is defined as the interval between the start date of treatment and the date of radiological disease progression or death due to any cause, whichever occurs first. Participants who did not progress in their disease were censored on the date of their last radiological assessment preceding the start of any additional anti-cancer therapy. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at a subsequent assessment made no less than 28 days after the original response.
Time Frame From the start date of treatment until the date of radiological disease progression or death due to any cause, whichever occurs first (up to Week 86)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib Plus Paclitaxel
Hide Arm/Group Description:
Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 57
Median (95% Confidence Interval)
Unit of Measure: weeks
IRC
47.9 [1] 
(40.0 to NA)
Investigator
50.9
(47.0 to 64.3)
[1]
The upper limit of the 95% confidence interval could not be determined (not reached) because there were not enough events to be able to calculate it.
9.Secondary Outcome
Title Overall Survival
Hide Description Overall survival is defined as the interval between the date of treatment start and the date of death due to any cause. For participants who did not die, follow-up was censored as the date of last contact. For participants who did not die, follow-up was censored at the date of last contact.
Time Frame From the date of the first dose until the date of death due to any cause (up to Week 86)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib Plus Paclitaxel
Hide Arm/Group Description:
Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 57
Median (95% Confidence Interval)
Unit of Measure: weeks
NA [1] 
(NA to NA)
[1]
At the time of this analysis, the median and the 95% confidence interval could not be determined because there were not enough deaths to calculate these estimates.
10.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Hide Description An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations.
Time Frame From the start of study medication until 28 days after the last dose (up to Study Week 381)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib Plus Paclitaxel
Hide Arm/Group Description:
Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed 57
Measure Type: Number
Unit of Measure: Participants
Any AE 57
Any SAE 11
Time Frame Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381).
Adverse Event Reporting Description SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
 
Arm/Group Title Lapatinib Plus Paclitaxel
Hide Arm/Group Description Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
All-Cause Mortality
Lapatinib Plus Paclitaxel
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Lapatinib Plus Paclitaxel
Affected / at Risk (%)
Total   11/57 (19.30%) 
Blood and lymphatic system disorders   
Neutropenia  1  4/57 (7.02%) 
Cardiac disorders   
Cardiopulmonary failure  1  1/57 (1.75%) 
Gastrointestinal disorders   
Diarrhoea  1  2/57 (3.51%) 
Infections and infestations   
Abscess limb  1  1/57 (1.75%) 
Abscess soft tissue  1  1/57 (1.75%) 
Upper respiratory tract infection  1  1/57 (1.75%) 
Metabolism and nutrition disorders   
Dehydration  1  1/57 (1.75%) 
Respiratory, thoracic and mediastinal disorders   
Bronchospasm  1  1/57 (1.75%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lapatinib Plus Paclitaxel
Affected / at Risk (%)
Total   56/57 (98.25%) 
Blood and lymphatic system disorders   
Neutropenia  1  25/57 (43.86%) 
Leukopenia  1  10/57 (17.54%) 
Anaemia  1  9/57 (15.79%) 
Gastrointestinal disorders   
Diarrhoea  1  32/57 (56.14%) 
Abdominal pain upper  1  9/57 (15.79%) 
Nausea  1  9/57 (15.79%) 
Vomiting  1  6/57 (10.53%) 
General disorders   
Fatigue  1  15/57 (26.32%) 
Oedema peripheral  1  6/57 (10.53%) 
Asthenia  1  5/57 (8.77%) 
Hepatobiliary disorders   
Hyperbilirubinaemia  1  3/57 (5.26%) 
Immune system disorders   
Hypersensitivity  1  4/57 (7.02%) 
Infections and infestations   
Upper respiratory tract infection  1  6/57 (10.53%) 
Erysipelas  1  5/57 (8.77%) 
Paronychia  1  3/57 (5.26%) 
Respiratory tract infection  1  3/57 (5.26%) 
Investigations   
Alanine aminotransferase increased  1  10/57 (17.54%) 
Aspartate aminotransferase increased  1  5/57 (8.77%) 
Weight decreased  1  4/57 (7.02%) 
Metabolism and nutrition disorders   
Hypokalaemia  1  5/57 (8.77%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  6/57 (10.53%) 
Bone pain  1  4/57 (7.02%) 
Nervous system disorders   
Peripheral sensory neuropathy  1  14/57 (24.56%) 
Neuropathy peripheral  1  8/57 (14.04%) 
Dizziness  1  6/57 (10.53%) 
Headache  1  3/57 (5.26%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  5/57 (8.77%) 
Epistaxis  1  4/57 (7.02%) 
Skin and subcutaneous tissue disorders   
Rash  1  23/57 (40.35%) 
Alopecia  1  9/57 (15.79%) 
Nail disorder  1  6/57 (10.53%) 
Nail dystrophy  1  3/57 (5.26%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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
Publications:
Jagiello-Gruszfeld A, Tjulandin Sergei S, Dobrovolskaya N et al, Lapatinib (L) with weekly paclitaxel (P) as first-line therapy for patients (pts) with HER2+ metastatic breast cancer (MBC). The 31st Annual San Antonio Breast Cancer Symposium; San Antonio TX: December 10-14 2008. Abstract 3145.
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00356811     History of Changes
Other Study ID Numbers: EGF105764
First Submitted: July 25, 2006
First Posted: July 26, 2006
Results First Submitted: May 8, 2014
Results First Posted: July 21, 2014
Last Update Posted: July 21, 2014