Paclitaxel With / Without GW572016 (Lapatinib) As First Line Therapy For Women With Advanced Or Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00075270
First received: January 7, 2004
Last updated: February 13, 2014
Last verified: December 2013
Results First Received: March 14, 2013  
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: Paclitaxel
Drug: GW572016 (Lapatinib)

  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
A total of 580 participants were enrolled and randomized to treatment; however one participant withdrew from the study before taking any medication. Thus, only 579 participants were included in the Intent-to-Treat Population (comprised of all randomized participants who had received at least one dose of randomized therapy [lapatinib or placebo]).

Reporting Groups
  Description
Lapatinib With Paclitaxel Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Placebo With Paclitaxel Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.

Participant Flow:   Overall Study
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
STARTED     291     288  
Missing     26 [1]   13 [1]
COMPLETED     5     4  
NOT COMPLETED     286     284  
Withdrawal by Subject                 28                 21  
Lost to Follow-up                 25                 28  
Protocol Violation                 0                 2  
Death                 198                 215  
Other/Unknown                 9                 5  
Missing                 26                 13  
[1] These participants have no completion status information recorded on the case report forms.



  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 With Paclitaxel Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Placebo With Paclitaxel Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Total Total of all reporting groups

Baseline Measures
    Lapatinib With Paclitaxel     Placebo With Paclitaxel     Total  
Number of Participants  
[units: participants]
  291     288     579  
Age  
[units: Years]
Mean ± Standard Deviation
  51.3  ± 10.45     52.4  ± 10.98     51.8  ± 10.72  
Gender  
[units: Participants]
     
Female     291     288     579  
Male     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
     
White     190     182     372  
Black     10     10     20  
Asian     30     35     65  
American Hispanic     54     53     107  
Unknown     7     8     15  



  Outcome Measures
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1.  Primary:   Time to Progression as Evaluated by the Investigator   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]
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Measure Type Primary
Measure Title Time to Progression as Evaluated by the Investigator
Measure Description Time to progression (TTP) is defined as the interval between the date of randomization and the earliest date of progression of disease (PD) or death due to breast cancer. The investigator assessed PD based on radiological PD (imaging data) and clinical symptomatic progress (Response Evaluation Criteria in Solid Tumors [RECIST] Criteria: target lesion (TL), at least a 20% increase in the sum of largest diameter (LD) of TLs or the appearance of one or more new lesions; non-TL (NTL), the appearance of one or more new lesions and/or unequivocal progression of existing NTLs). TTP was assessed in participants who died due to breast cancer or progressed, as assessed by the investigator, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those without a documented date of disease progression/death due to breast cancer), the date of the last radiographic assessment was used.
Time Frame Randomization until the date of disease progression or death (average of 26 weeks)  
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 who had received at least one dose of randomized therapy (lapatinib or placebo)

Reporting Groups
  Description
Lapatinib With Paclitaxel Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Placebo With Paclitaxel Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Time to Progression as Evaluated by the Investigator  
[units: weeks]
Median ( Inter-Quartile Range )
  29.0  
  ( 13.9 to 46.9 )  
  22.9  
  ( 12.0 to 38.3 )  


Statistical Analysis 1 for Time to Progression as Evaluated by the Investigator
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.142
Hazard Ratio, log [4] 0.87
95% Confidence Interval ( 0.72 to 1.05 )
[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:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value from stratified log-rank test, stratifying for stage of disease and site of disease at screening
[4] Other relevant estimation information:
  The estimate of the treatment hazard ratio is based on the log-rank test.



2.  Primary:   Time to Progression as Evaluated by the Independent Review Committee (IRC)   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

3.  Secondary:   Number of Participants With Tumor Response as Evaluated by the Investigator   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

4.  Secondary:   Number of Participants With Tumor Response as Evaluated by the Independent Review Committee   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

5.  Secondary:   Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

6.  Secondary:   Number of Participants With a Response of CR or PR by the Indicated Study Week   [ Time Frame: Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, and 72 ]

7.  Secondary:   Duration of Response (DOR)   [ Time Frame: From the time of the first documented complete or partial response until the first documented evidence of progression or death (average of 26 weeks) ]

8.  Secondary:   Progression-Free Survival (PFS)   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

9.  Secondary:   Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS)   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

10.  Secondary:   Overall Survival   [ Time Frame: Randomization until the date of death due to any cause (average of 24 months) ]

11.  Secondary:   Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Scores   [ Time Frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal ]

12.  Secondary:   Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores   [ Time Frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal ]

13.  Secondary:   Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores   [ Time Frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal ]

14.  Secondary:   Number of Participants With the Indicated ErbB2 Status at Baseline   [ Time Frame: Baseline ]

15.  Secondary:   ErbB2 Ratio   [ Time Frame: Baseline ]

16.  Secondary:   Number of Participants With the Indicated Immunohistochemistry (IHC) Results at Screening   [ Time Frame: Screening (Day -1) ]

17.  Secondary:   Number of Participants With the Indicated ErbB2 Fluorescence in Situ Hybridization (FISH) Results   [ Time Frame: Baseline ]

18.  Secondary:   Serum ErbB1 Concentration   [ Time Frame: Screening (Day-1) and Withdrawal (up to Study Week 129) ]

19.  Secondary:   Serum ErbB2 Concentration   [ Time Frame: Screening (Day-1) and Withdrawal (up to Study Week 129) ]

20.  Secondary:   Number of Participants With the Indicated Adverse Events (AEs) With a Maximum Toxicity Grade of 3 or 4   [ Time Frame: Baseline (Day 1) until 30 days after the last dose of randomized therapy (average of 26 weeks) ]


  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
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  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:
Publications automatically indexed to this study:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00075270     History of Changes
Obsolete Identifiers: NCT00085046
Other Study ID Numbers: EGF30001
Study First Received: January 7, 2004
Results First Received: March 14, 2013
Last Updated: February 13, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration