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Lapatinib in Combination With Vinorelbine (VITAL)

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ClinicalTrials.gov Identifier: NCT01013740
Recruitment Status : Completed
First Posted : November 16, 2009
Results First Posted : July 18, 2013
Last Update Posted : May 31, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cancer
Interventions Drug: Vinorelbine
Drug: Lapatinib
Drug: Capecitabine
Enrollment 112
Recruitment Details  
Pre-assignment Details In the Randomized Phase (RP), participants were treated until disease progression (PD) or discontinuation of treatment due to unacceptable toxicity, withdrawal of consent, lost to follow-up, or death. After PD in the RP, participants were given the option of crossing over to the alternative treatment arm in a post-progression Cross-over Phase (CP).
Arm/Group Title Lapatinib + Capecitabine in RP; Lapatinib + Vinorelbine in CP Lapatinib + Vinorelbine in RP; Lapatinib + Capecitabine in CP
Hide Arm/Group Description Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) continuously at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food with approximately 200 milliliters (mL) of water. After disease progression in the Randomized Phase (in which participants received lapatinib plus vinorelbine), participants were given the option of crossing over to the alternative treatment arm (lapatinib plus capecitabine), and continuing in a post-progression Cross-over Phase. Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received an intravenous (IV) infusion of vinorelbine 20 mg/m^2 over the course of 5 to 10 minutes on Days 1 and 8 of a 21-day treatment cycle. After disease progression in the Randomized Phase (in which participants received lapatinib plus capecitabine), participants were given the option of crossing over to the alternative treatment arm (lapatinib plus vinorelbine), and continuing in a post-progression Cross-over Phase.
Period Title: Overall Study
Started 37 [1] 75 [2]
Ongoing 0 0
Completed 26 [3] 56 [3]
Not Completed 11 19
Reason Not Completed
Lost to Follow-up             3             5
Physician Decision             2             0
Withdrawal by Subject             2             10
study close / terminated : done in error             2             1
Missing             2             1
Ongoing: Study records not completed             0             2
[1]
13 participants (par.) experiencing PD in the RP elected to enroll in the optional CP.
[2]
29 participants experiencing PD in the RP elected to enroll in the optional CP.
[3]
Completion also = 18 mos.of a new anti-cancer therapy initiation +/or progression of disease
Arm/Group Title Lapatinib + Capecitabine in RP; Lapatinib + Vinorelbine in CP Lapatinib + Vinorelbine in RP; Lapatinib + Capecitabine in CP Total
Hide Arm/Group Description Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) continuously at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food with approximately 200 milliliters (mL) of water. After disease progression in the Randomized Phase (in which participants received lapatinib plus vinorelbine), participants were given the option of crossing over to the alternative treatment arm (lapatinib plus capecitabine), and continuing in a post-progression Cross-over Phase. Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received an intravenous (IV) infusion of vinorelbine 20 mg/m^2 over the course of 5 to 10 minutes on Days 1 and 8 of a 21-day treatment cycle. After disease progression in the Randomized Phase (in which participants received lapatinib plus capecitabine), participants were given the option of crossing over to the alternative treatment arm (lapatinib plus vinorelbine), and continuing in a post-progression Cross-over Phase. Total of all reporting groups
Overall Number of Baseline Participants 37 75 112
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 37 participants 75 participants 112 participants
57.5  (10.90) 57.7  (10.23) 57.6  (10.41)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 75 participants 112 participants
Female
37
 100.0%
75
 100.0%
112
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 37 participants 75 participants 112 participants
White 36 74 110
Native Hawaiian or other Pacific Islander & White 1 0 1
African American/African Heritage 0 1 1
1.Primary Outcome
Title Progression Free Survival (PFS) in the Randomized Phase
Hide Description PFS is defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause, if sooner. PD is defined as at least a 20 % increase in the sum of the longest diameter (LD) of target lesions, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of >=1 new lesion.
Time Frame From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: participants who were randomized to study treatment, regardless of whether they actually received study medication
Arm/Group Title Lapatinib Plus Capecitabine Lapatinib Plus Vinorelbine
Hide Arm/Group Description:
Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) continuously at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food with approximately 200 milliliters (mL) of water.
Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received an intravenous (IV) infusion of vinorelbine 20 mg/m^2 over the course of 5 to 10 minutes on Days 1 and 8 of a 21-day treatment cycle.
Overall Number of Participants Analyzed 37 75
Median (95% Confidence Interval)
Unit of Measure: months
6.2
(4.4 to 8.3)
6.2
(4.2 to 8.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lapatinib Plus Capecitabine, Lapatinib Plus Vinorelbine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.84
Confidence Interval 95%
0.53 to 1.35
Estimation Comments The Pike estimator of the treatment HR was based on the log rank test.
2.Secondary Outcome
Title Number of Participants With Overall Response (OR), as Assessed by the Investigator in the Randomized Phase
Hide Description OR is defined as the number of participants achieving either a confirmed complete response (CR: the disappearance of all target lesions [TLs]) or partial response (PR: a >=30% decrease in the sum of the longest diameter [LD] of the TLs, taking as reference the baseline sum LD) as assessed by the investigator as the best OR.
Time Frame From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib Plus Capecitabine Lapatinib Plus Vinorelbine
Hide Arm/Group Description:
Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) continuously at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food with approximately 200 milliliters (mL) of water.
Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received an intravenous (IV) infusion of vinorelbine 20 mg/m^2 over the course of 5 to 10 minutes on Days 1 and 8 of a 21-day treatment cycle.
Overall Number of Participants Analyzed 37 75
Measure Type: Number
Unit of Measure: participants
13 15
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the time from randomization to the date of death due to any cause. Participants who had not died were censored at the date of the last adequate tumor assessment at the time of the cut-off.
Time Frame From the date of randomization until death (average of 55 study weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib Plus Capecitabine Lapatinib Plus Vinorelbine
Hide Arm/Group Description:
Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) continuously at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food with approximately 200 milliliters (mL) of water.
Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received an intravenous (IV) infusion of vinorelbine 20 mg/m^2 over the course of 5 to 10 minutes on Days 1 and 8 of a 21-day treatment cycle.
Overall Number of Participants Analyzed 37 75
Median (95% Confidence Interval)
Unit of Measure: months
19.4
(16.4 to 27.2)
24.3 [1] 
(16.4 to NA)
[1]
The upper limit of the 95% confidence interval (CI) could not be determined (not reached) because there were not enough events to be able to calculate the upper limit of the CI.
4.Secondary Outcome
Title Duration of Response (DOR) in the Randomized Phase
Hide Description DOR is defined as the time from the first documented evidence of response (CR or PR) until the first documented sign of disease progression (a >=20% increase in the sum of the LD of TLs, taking as reference the smallest sum LD recorded since the treatment started or the appearance of >=1 new lesion) or death, if sooner. CR=the disappearance of all TLs. PR=a >=30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD.
Time Frame From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (average of 27 study weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only participants with a confirmed CR or PR were assessed for duration of response.
Arm/Group Title Lapatinib Plus Capecitabine Lapatinib Plus Vinorelbine
Hide Arm/Group Description:
Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) continuously at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food with approximately 200 milliliters (mL) of water.
Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received an intravenous (IV) infusion of vinorelbine 20 mg/m^2 over the course of 5 to 10 minutes on Days 1 and 8 of a 21-day treatment cycle.
Overall Number of Participants Analyzed 13 15
Median (95% Confidence Interval)
Unit of Measure: months
10.8 [1] 
(4.3 to NA)
6.7
(4.6 to 8.3)
[1]
The upper limit of the 95% confidence interval (CI) could not be determined (not reached) because there were not enough events to be able to calculate the upper limit of the CI.
5.Secondary Outcome
Title Time to Response in the Randomized Phase
Hide Description Time to response is defined as the time from randomization until the first documented evidence of CR (the disappearance of all TLs) or PR (a >=30% decrease in the sum of the LD of the TLs, taking as a reference the basline sum LD) (whichever status is recorded first). When tumor response was confirmed at a repeat assessment, the time to response was taken to be the first time that the response was observed.
Time Frame From randomization until the time of the first documented confirmed CR or PR (average of 27 study weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only participants with a confirmed CR or PR were assessed for time to response.
Arm/Group Title Lapatinib Plus Capecitabine Lapatinib Plus Vinorelbine
Hide Arm/Group Description:
Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) continuously at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food with approximately 200 milliliters (mL) of water.
Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received an intravenous (IV) infusion of vinorelbine 20 mg/m^2 over the course of 5 to 10 minutes on Days 1 and 8 of a 21-day treatment cycle.
Overall Number of Participants Analyzed 13 15
Median (95% Confidence Interval)
Unit of Measure: weeks
9.3
(9.1 to 10.0)
9.4
(9.0 to 10.1)
6.Secondary Outcome
Title Number of Participants With Clinical Benefit (CB) in the Randomized Phase
Hide Description CB is defined as the the number of participants achieving either a confirmed CR or PR or having stable disease (SD) for at least 24 weeks (i.e., approximately 6 months). CR=the disappearance of all TLs. PR=a >=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD=at least a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of >=1 new lesion). Participants with unknown or missing responses were treated as non-responders.
Time Frame From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib Plus Capecitabine Lapatinib Plus Vinorelbine
Hide Arm/Group Description:
Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) continuously at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food with approximately 200 milliliters (mL) of water.
Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received an intravenous (IV) infusion of vinorelbine 20 mg/m^2 over the course of 5 to 10 minutes on Days 1 and 8 of a 21-day treatment cycle.
Overall Number of Participants Analyzed 37 75
Measure Type: Number
Unit of Measure: participants
18 29
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lapatinib Plus Capecitabine, Lapatinib Plus Vinorelbine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.50
Confidence Interval (2-Sided) 95%
0.63 to 3.58
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Area Under the Concentration-time Curve Over the Dosing Interval (AUC-tau) for Vinorelbine
Hide Description AUC-tau is defined as the area under the concentration-time curve over a dosing interval at steady state, where tau is the length of the dosing interval. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. Pharmacokinetic (PK) parameters were to be assessed in an optional sub-study. No participants were enrolled in this optional sub-study; thus, no PK data are available.
Time Frame Days 1 and 8; 0 to 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lapatinib Plus Capecitabine Lapatinib Plus Vinorelbine
Hide Arm/Group Description:
Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) continuously at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food with approximately 200 milliliters (mL) of water.
Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received an intravenous (IV) infusion of vinorelbine 20 mg/m^2 over the course of 5 to 10 minutes on Days 1 and 8 of a 21-day treatment cycle.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Maximum Concentration (Cmax) for Vinorelbine
Hide Description Cmax is defined as the maximum observed plasma or serum concentration after administration of the drug. PK parameters were to be assessed in an optional sub-study. No participants were enrolled in this optional sub-study; thus, no PK data are available.
Time Frame Days 1 and 8; 0 to 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lapatinib Plus Capecitabine Lapatinib Plus Vinorelbine
Hide Arm/Group Description:
Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) continuously at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food with approximately 200 milliliters (mL) of water.
Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received an intravenous (IV) infusion of vinorelbine 20 mg/m^2 over the course of 5 to 10 minutes on Days 1 and 8 of a 21-day treatment cycle.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Number of Participants With Grade 4 and Grade 5 Adverse Events (AE)
Hide Description An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grades: 0 = no AE or within normal limits; 1 = mild AE; 2 = moderate AE; 3 = severe and undesirable AE; 4 = life-threatening or disabling AE; 5 = death related to AE.
Time Frame From randomization until disease progression, death, or discontinuation from the study (average of 55 study weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: participants who received at least one dose of study medication, based on the actual treatment received
Arm/Group Title Lapatinib Plus Capecitabine Lapatinib Plus Vinorelbine
Hide Arm/Group Description:
Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) continuously at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food with approximately 200 milliliters (mL) of water.
Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before food or 1 hour (or more) after food. Participants also received an intravenous (IV) infusion of vinorelbine 20 mg/m^2 over the course of 5 to 10 minutes on Days 1 and 8 of a 21-day treatment cycle.
Overall Number of Participants Analyzed 37 75
Measure Type: Number
Unit of Measure: participants
Helicobacter gastritis, Grade 4 1 0
Neutropenia, Grade 4 0 9
Leukopenia, Grade 4 0 1
Febrile neutropenia, Grade 4 0 1
Mucosal inflammation, Grade 4 0 1
Pulmonary embolism, Grade 4 0 1
Intestinal obstruction, Grade 5 0 1
Time Frame Serious Adverse Events are monitored from date of First Subject First Visit (FSFV) until Last Subject Last Visit (LSLV). All other adverse events are monitored from First Subject First Treatment until LSLV. Initiation Date: 25 November 2009- Completion Date: 21 August 2012
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Randomized Phase Lapatinib 1250mg QD + Capecitabine 2000mg/m2 Randomized Phase Lapatinib 1250mg QD + Vinorelbine 20mg/m2 Crossover Phase Lapatinib 1250mg QD + Capecitabine 2000mg/m2 Crossover Phase Lapatinib 1250mg QD + Vinorelbine 20mg/m2
Hide Arm/Group Description Randomized phase Lapatinib 1250mg QD + Capecitabine 2000mg/m2 Randomized phase Lapatinib 1250mg QD + Vinorelbine 20mg/m2 Crossover phase Lapatinib 1250mg QD + Capecitabine 2000mg/m2 Crossover phase Lapatinib 1250mg QD + Vinorelbine 20mg/m2
All-Cause Mortality
Randomized Phase Lapatinib 1250mg QD + Capecitabine 2000mg/m2 Randomized Phase Lapatinib 1250mg QD + Vinorelbine 20mg/m2 Crossover Phase Lapatinib 1250mg QD + Capecitabine 2000mg/m2 Crossover Phase Lapatinib 1250mg QD + Vinorelbine 20mg/m2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Randomized Phase Lapatinib 1250mg QD + Capecitabine 2000mg/m2 Randomized Phase Lapatinib 1250mg QD + Vinorelbine 20mg/m2 Crossover Phase Lapatinib 1250mg QD + Capecitabine 2000mg/m2 Crossover Phase Lapatinib 1250mg QD + Vinorelbine 20mg/m2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/37 (10.81%)   25/75 (33.33%)   3/37 (8.11%)   4/17 (23.53%) 
Blood and lymphatic system disorders         
Anaemia  1  0/37 (0.00%)  2/75 (2.67%)  0/37 (0.00%)  0/17 (0.00%) 
Febrile neutropenia  1  0/37 (0.00%)  2/75 (2.67%)  0/37 (0.00%)  2/17 (11.76%) 
Leukopenia  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Neutropenia  1  0/37 (0.00%)  10/75 (13.33%)  0/37 (0.00%)  1/17 (5.88%) 
Cardiac disorders         
Arrhythmia  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Gastrointestinal disorders         
Abdominal pain  1  1/37 (2.70%)  0/75 (0.00%)  0/37 (0.00%)  0/17 (0.00%) 
Diarrhoea  1  1/37 (2.70%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Intestinal obstruction  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Vomiting  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
General disorders         
Fatigue  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Pyrexia  1  0/37 (0.00%)  2/75 (2.67%)  1/37 (2.70%)  0/17 (0.00%) 
Hepatobiliary disorders         
Cholecystitis acute  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Cholestasis  1  0/37 (0.00%)  0/75 (0.00%)  1/37 (2.70%)  0/17 (0.00%) 
Liver injury  1  0/37 (0.00%)  0/75 (0.00%)  1/37 (2.70%)  0/17 (0.00%) 
Infections and infestations         
Helicobacter gastritis  1  1/37 (2.70%)  0/75 (0.00%)  0/37 (0.00%)  0/17 (0.00%) 
Herpes zoster  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Infection  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Lymphangitis  1  0/37 (0.00%)  1/75 (1.33%)  1/37 (2.70%)  0/17 (0.00%) 
Respiratory tract infection  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Urinary tract infection  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Injury, poisoning and procedural complications         
Femur fracture  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Investigations         
Ejection fraction decreased  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Metastases to central nervous system  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  1/17 (5.88%) 
Nervous system disorders         
Paraplegia  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Peripheral motor neuropathy  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Peripheral sensory neuropathy  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Product Issues         
Device leakage  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Pulmonary embolism  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Vascular disorders         
Lymphoedema  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Thrombosis  1  1/37 (2.70%)  0/75 (0.00%)  0/37 (0.00%)  0/17 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Randomized Phase Lapatinib 1250mg QD + Capecitabine 2000mg/m2 Randomized Phase Lapatinib 1250mg QD + Vinorelbine 20mg/m2 Crossover Phase Lapatinib 1250mg QD + Capecitabine 2000mg/m2 Crossover Phase Lapatinib 1250mg QD + Vinorelbine 20mg/m2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   32/37 (86.49%)   72/75 (96.00%)   27/37 (72.97%)   15/17 (88.24%) 
Blood and lymphatic system disorders         
Anaemia  1  2/37 (5.41%)  13/75 (17.33%)  2/37 (5.41%)  2/17 (11.76%) 
Febrile neutropenia  1  0/37 (0.00%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Leukopenia  1  3/37 (8.11%)  11/75 (14.67%)  1/37 (2.70%)  2/17 (11.76%) 
Neutropenia  1  3/37 (8.11%)  34/75 (45.33%)  2/37 (5.41%)  7/17 (41.18%) 
Thrombocytopenia  1  0/37 (0.00%)  3/75 (4.00%)  2/37 (5.41%)  1/17 (5.88%) 
Cardiac disorders         
Tachycardia  1  2/37 (5.41%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Eye disorders         
Ophthalmoplegia  1  0/37 (0.00%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Gastrointestinal disorders         
Abdominal pain  1  2/37 (5.41%)  7/75 (9.33%)  1/37 (2.70%)  0/17 (0.00%) 
Abdominal pain upper  1  1/37 (2.70%)  6/75 (8.00%)  0/37 (0.00%)  0/17 (0.00%) 
Constipation  1  2/37 (5.41%)  6/75 (8.00%)  0/37 (0.00%)  0/17 (0.00%) 
Diarrhoea  1  21/37 (56.76%)  35/75 (46.67%)  7/37 (18.92%)  1/17 (5.88%) 
Dyspepsia  1  0/37 (0.00%)  6/75 (8.00%)  1/37 (2.70%)  0/17 (0.00%) 
Flatulence  1  1/37 (2.70%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Mouth ulceration  1  0/37 (0.00%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Nausea  1  3/37 (8.11%)  20/75 (26.67%)  6/37 (16.22%)  0/17 (0.00%) 
Stomatitis  1  0/37 (0.00%)  1/75 (1.33%)  1/37 (2.70%)  1/17 (5.88%) 
Vomiting  1  4/37 (10.81%)  13/75 (17.33%)  0/37 (0.00%)  0/17 (0.00%) 
General disorders         
Asthenia  1  5/37 (13.51%)  10/75 (13.33%)  3/37 (8.11%)  0/17 (0.00%) 
Axillary pain  1  0/37 (0.00%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Fatigue  1  3/37 (8.11%)  17/75 (22.67%)  1/37 (2.70%)  2/17 (11.76%) 
Inflammation  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  1/17 (5.88%) 
Influenza like illness  1  0/37 (0.00%)  2/75 (2.67%)  0/37 (0.00%)  1/17 (5.88%) 
Injection site reaction  1  0/37 (0.00%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Mucosal inflammation  1  0/37 (0.00%)  9/75 (12.00%)  1/37 (2.70%)  0/17 (0.00%) 
Oedema peripheral  1  1/37 (2.70%)  7/75 (9.33%)  0/37 (0.00%)  0/17 (0.00%) 
Peripheral swelling  1  0/37 (0.00%)  0/75 (0.00%)  1/37 (2.70%)  1/17 (5.88%) 
Pyrexia  1  1/37 (2.70%)  10/75 (13.33%)  2/37 (5.41%)  2/17 (11.76%) 
Hepatobiliary disorders         
Hepatotoxicity  1  0/37 (0.00%)  0/75 (0.00%)  1/37 (2.70%)  1/17 (5.88%) 
Hyperbilirubinaemia  1  6/37 (16.22%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Infections and infestations         
Abscess  1  0/37 (0.00%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Bronchitis  1  1/37 (2.70%)  4/75 (5.33%)  0/37 (0.00%)  1/17 (5.88%) 
Cystitis  1  1/37 (2.70%)  2/75 (2.67%)  1/37 (2.70%)  1/17 (5.88%) 
Herpes zoster  1  1/37 (2.70%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Nasopharyngitis  1  1/37 (2.70%)  4/75 (5.33%)  1/37 (2.70%)  0/17 (0.00%) 
Oral herpes  1  0/37 (0.00%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Paronychia  1  5/37 (13.51%)  2/75 (2.67%)  2/37 (5.41%)  0/17 (0.00%) 
Pharyngitis  1  1/37 (2.70%)  1/75 (1.33%)  0/37 (0.00%)  1/17 (5.88%) 
Sinusitis  1  0/37 (0.00%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Subcutaneous abscess  1  0/37 (0.00%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Upper respiratory tract infection  1  2/37 (5.41%)  5/75 (6.67%)  1/37 (2.70%)  0/17 (0.00%) 
Investigations         
Alanine aminotransferase increased  1  3/37 (8.11%)  8/75 (10.67%)  4/37 (10.81%)  2/17 (11.76%) 
Aspartate aminotransferase increased  1  4/37 (10.81%)  8/75 (10.67%)  5/37 (13.51%)  2/17 (11.76%) 
Blood alkaline phosphatase increased  1  1/37 (2.70%)  4/75 (5.33%)  3/37 (8.11%)  1/17 (5.88%) 
Blood bilirubin increased  1  4/37 (10.81%)  0/75 (0.00%)  1/37 (2.70%)  1/17 (5.88%) 
Blood calcium increased  1  0/37 (0.00%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Gamma-glutamyltransferase increased  1  0/37 (0.00%)  5/75 (6.67%)  0/37 (0.00%)  0/17 (0.00%) 
Weight decreased  1  2/37 (5.41%)  4/75 (5.33%)  1/37 (2.70%)  0/17 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite  1  2/37 (5.41%)  12/75 (16.00%)  2/37 (5.41%)  0/17 (0.00%) 
Hypercalcaemia  1  0/37 (0.00%)  1/75 (1.33%)  0/37 (0.00%)  1/17 (5.88%) 
Hypoalbuminaemia  1  0/37 (0.00%)  4/75 (5.33%)  0/37 (0.00%)  0/17 (0.00%) 
Hypocalcaemia  1  2/37 (5.41%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Hypochloraemia  1  0/37 (0.00%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Hypokalaemia  1  1/37 (2.70%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  3/37 (8.11%)  9/75 (12.00%)  1/37 (2.70%)  0/17 (0.00%) 
Back pain  1  1/37 (2.70%)  7/75 (9.33%)  0/37 (0.00%)  0/17 (0.00%) 
Bone pain  1  2/37 (5.41%)  7/75 (9.33%)  0/37 (0.00%)  3/17 (17.65%) 
Myalgia  1  0/37 (0.00%)  5/75 (6.67%)  2/37 (5.41%)  0/17 (0.00%) 
Neck pain  1  2/37 (5.41%)  1/75 (1.33%)  0/37 (0.00%)  0/17 (0.00%) 
Pain in extremity  1  3/37 (8.11%)  8/75 (10.67%)  4/37 (10.81%)  2/17 (11.76%) 
Nervous system disorders         
Dizziness  1  0/37 (0.00%)  5/75 (6.67%)  2/37 (5.41%)  0/17 (0.00%) 
Headache  1  2/37 (5.41%)  8/75 (10.67%)  2/37 (5.41%)  2/17 (11.76%) 
Neuropathy peripheral  1  0/37 (0.00%)  5/75 (6.67%)  2/37 (5.41%)  0/17 (0.00%) 
Paraesthesia  1  2/37 (5.41%)  2/75 (2.67%)  0/37 (0.00%)  0/17 (0.00%) 
Peripheral sensory neuropathy  1  0/37 (0.00%)  8/75 (10.67%)  0/37 (0.00%)  0/17 (0.00%) 
Psychiatric disorders         
Insomnia  1  2/37 (5.41%)  4/75 (5.33%)  0/37 (0.00%)  1/17 (5.88%) 
Reproductive system and breast disorders         
Vaginal inflammation  1  2/37 (5.41%)  0/75 (0.00%)  0/37 (0.00%)  0/17 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  1/37 (2.70%)  9/75 (12.00%)  0/37 (0.00%)  2/17 (11.76%) 
Dyspnoea  1  3/37 (8.11%)  4/75 (5.33%)  2/37 (5.41%)  1/17 (5.88%) 
Epistaxis  1  2/37 (5.41%)  3/75 (4.00%)  1/37 (2.70%)  0/17 (0.00%) 
Haemoptysis  1  0/37 (0.00%)  0/75 (0.00%)  1/37 (2.70%)  1/17 (5.88%) 
Oropharyngeal pain  1  2/37 (5.41%)  0/75 (0.00%)  0/37 (0.00%)  1/17 (5.88%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  1/37 (2.70%)  6/75 (8.00%)  0/37 (0.00%)  1/17 (5.88%) 
Erythema  1  2/37 (5.41%)  1/75 (1.33%)  1/37 (2.70%)  0/17 (0.00%) 
Nail disorder  1  4/37 (10.81%)  2/75 (2.67%)  1/37 (2.70%)  0/17 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  24/37 (64.86%)  6/75 (8.00%)  18/37 (48.65%)  0/17 (0.00%) 
Rash  1  5/37 (13.51%)  15/75 (20.00%)  2/37 (5.41%)  1/17 (5.88%) 
Skin fissures  1  2/37 (5.41%)  2/75 (2.67%)  0/37 (0.00%)  0/17 (0.00%) 
Vascular disorders         
Hot flush  1  0/37 (0.00%)  2/75 (2.67%)  0/37 (0.00%)  1/17 (5.88%) 
Indicates events were collected by systematic assessment
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Term from vocabulary, MedDRA (19.0)
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.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Clinical Disclosure Office
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01013740     History of Changes
Other Study ID Numbers: CLAP016A2205 / 112620
First Submitted: October 29, 2009
First Posted: November 16, 2009
Results First Submitted: February 28, 2013
Results First Posted: July 18, 2013
Last Update Posted: May 31, 2017