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Study In Women And Men With Metastatic Breast Cancer That Have Overexpression Of ErbB2

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00281658
First received: January 23, 2006
Last updated: July 28, 2016
Last verified: July 2016
Results First Received: May 5, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Neoplasms, Breast
Interventions: Drug: lapatinib (GW572016) oral tablets
Drug: paclitaxel infusion

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
At the time of disease progression, participants had the option to be unblinded. Participants (pts) who were on placebo+paclitaxel could continue in an open-label lapatinib monotherapy extension phase until further progression or an unacceptable toxicity. All participants were followed for survival. The unblinding was performed by a third party.

Reporting Groups
  Description
Lapatinib Plus Paclitaxel Lapatinib 1500 milligrams (mg) administered once daily plus paclitaxel 80 mg/meters squared (m^2) administered intravenously (IV) weekly for 3 weeks every 4 weeks
Placebo Plus Paclitaxel Matching placebo administered once daily plus paclitaxel 80 mg/m^2 administered IV weekly for 3 weeks every 4 weeks
Lapatinib 1500 mg Lapatinib 1500 mg administered once daily

Participant Flow for 2 periods

Period 1:   Double-blind, Randomized Phase
    Lapatinib Plus Paclitaxel   Placebo Plus Paclitaxel   Lapatinib 1500 mg
STARTED   222   222 [1]   0 
COMPLETED   85 [2]   168 [2]   0 
NOT COMPLETED   137   54   0 
Death                120                46                0 
Lost to Follow-up                12                5                0 
Withdrawal by Subject                4                1                0 
Participant Entered New Protocol                1                1                0 
Screen Failure; Randomized in Error                0                1                0 
[1] Of these participants, 149 entered the open-label extension phase.
[2] For the purposes of this report, completed pts are pts ongoing at the time of the analysis.

Period 2:   Open-label Monotherapy Extension Phase
    Lapatinib Plus Paclitaxel   Placebo Plus Paclitaxel   Lapatinib 1500 mg
STARTED   0   0   149 
COMPLETED   0   0   48 [1] 
NOT COMPLETED   0   0   101 
Death                0                0                97 
Lost to Follow-up                0                0                3 
Withdrawal by Subject                0                0                1 
[1] For the purposes of this report, completed pts are pts ongoing at the time of the analysis.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Lapatinib Plus Paclitaxel Lapatinib 1500 milligrams (mg) administered once daily plus paclitaxel 80 mg/meters squared (m^2) administered intravenously (IV) weekly for 3 weeks every 4 weeks
Placebo Plus Paclitaxel Matching placebo administered once daily plus paclitaxel 80 mg/m^2 administered IV weekly for 3 weeks every 4 weeks
Total Total of all reporting groups

Baseline Measures
    Lapatinib Plus Paclitaxel   Placebo Plus Paclitaxel   Total
Overall Participants Analyzed 
[Units: Participants]
 222   222   444 
Age 
[Units: Years]
Mean (Standard Deviation)
 49.1  (10.74)   49.3  (9.75)   49.2  (10.25) 
Gender 
[Units: Participants]
     
Female   222   217   439 
Male   0   5   5 
Race/Ethnicity, Customized 
[Units: Participants]
     
White   9   13   22 
Asian   192   192   384 
Hispanic   21   16   37 
Missing   0   1   1 
Number of participants with any visceral metastatic disease and with only non-visceral disease [1] 
[Units: Participants]
     
Visceral   187   186   373 
Non-visceral   35   36   71 
[1] Metastasis is defined as the spread of a tumor or cancerous cells from the primary site to one or more sites elsewhere in the body. Visceral metastasis is defined as the spread of cancer to viscera, the internal organs of the body, specifically those within the chest (as the heart or lungs) or abdomen (as the liver, pancreas, or intestines). Non-visceral organs are defined as any organ not considered visceral.
Number of Participants with the Indicated Hormone Receptor Status [1] 
[Units: Participants]
     
ER+ and/or PgR+ or Unknown   111   113   224 
ER- and PgR-   111   109   220 
[1] Cancer cells have hormone receptor expression of Estrogen Receptor (ER) and/or Progesterone Receptor (PR) and are thus considered to be ER+ and/or PgR+ cells, respectively.
Number of Participants with the Indicated Stage of Disease at Initial Diagnosis [1] 
[Units: Participants]
     
Stage I to II   107   119   226 
Stage III   75   68   143 
Stage IV   30   24   54 
Unknown   10   11   21 
[1] The stage of cancer is a description of the extent to which the cancer has spread. Stage I cancer is localized; Stage II cancer has not started to spread into the surrounding tissue, but the tumor is larger than in Stage I; Stage III cancer is locally advanced and/or involves local lymph nodes; Stage IV cancer has spread to other organs.
Number of Participants with the Indicated Eastern Cooperative Oncology Group Performance Status [1] 
[Units: Participants]
     
0, Fully Active   103   113   216 
1, Ambulatory, Restricted Strenuous Activity   119   109   228 
[1] Eastern Cooperative Oncology Group (ECOG) Performance Status classifies participants according to their functional impairment, and scores indicate: 0, fully active; 1, ambulatory, restricted strenuous activity; 2, ambulatory, no work activity; 3, partially confined to bed; 5, death. Participants were required to have a baseline ECOG performance status of 0 or 1 for study participation.
Number of Participants with the Indicated Number of Metastatic Sites [1] 
[Units: Participants]
     
Greater than or equal to 3   131   115   246 
Less than 3   91   107   198 
[1] Tumor cells move from the primary site to other sites in the body, where they continue to multiply and eventually form another clinically detectable tumor; thus, the site becomes metastatic.
Number of Participants in the Indicated Age Groups 
[Units: Participants]
     
Greater than or equal to 65 years of age   16   13   29 
Less than 65 years of age   206   209   415 
Mean Time of Disease-Free Interval [1] 
[Units: Months]
Mean (Standard Deviation)
 27.51  (27.481)   29.04  (34.522)   28.27  (31.174) 
[1] The disease-free interval was defined as the time from initial diagnosis to metastases.


  Outcome Measures
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1.  Primary:   Overall Survival   [ Time Frame: Randomization to death (up to maximum of Month 53) ]
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Measure Type Primary
Measure Title Overall Survival
Measure Description Overall survival is defined as the time from randomization until death due to any cause.
Time Frame Randomization to death (up to maximum of Month 53)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants

Reporting Groups
  Description
Lapatinib Plus Paclitaxel Lapatinib 1500 milligrams (mg) administered once daily plus paclitaxel 80 mg/meters squared (m^2) administered intravenously (IV) weekly for 3 weeks every 4 weeks
Placebo Plus Paclitaxel Matching placebo administered once daily plus paclitaxel 80 mg/m^2 administered IV weekly for 3 weeks every 4 weeks

Measured Values
    Lapatinib Plus Paclitaxel   Placebo Plus Paclitaxel
Participants Analyzed 
[Units: Participants]
 222   222 
Overall Survival 
[Units: Months]
Median (95% Confidence Interval)
 27.8 
 (23.2 to 32.2) 
 20.5 
 (17.9 to 24.3) 


Statistical Analysis 1 for Overall Survival
Groups [1] All groups
Method [2] Wald Chi-squared
P Value [3] 0.0005
Hazard Ratio (HR) [4] 0.64
95% Confidence Interval 0.49 to 0.82
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for hormonal status, metastatic disease site, initial diagnosis stage, ECOG status, number of metastatic sites, age and disease-free interval
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  two-sided p-value
[4] Other relevant estimation information:
  Adjusted HR based on Cox Regression model

Statistical Analysis 2 for Overall Survival
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.0124
Hazard Ratio (HR) [4] 0.74
95% Confidence Interval 0.58 to 0.94
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified log-rank test, stratifying for metastatic disease sites and hormonal status
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  two-sided p-value
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Progression-free Survival   [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ]

3.  Secondary:   Overall Response (OR)   [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ]

4.  Secondary:   Clinical Benefit   [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ]

5.  Secondary:   Duration of Response   [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ]

6.  Secondary:   Number of Participants With a CR or PR at Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72   [ Time Frame: Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Some participants (PAR) are captured as withdrawing from the study due to death. Per protocol, PAR who died were considered to be study completers and did not withdraw from the study; for the purposes of this report, they are classified as withdrawn.


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