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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):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00281658
First received: January 23, 2006
Last updated: January 24, 2013
Last verified: January 2013
History of Changes
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
Conditions: Her2+
Metastatic Breast Cancer
Neoplasms, Breast
Cancer
ErbB2+
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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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  
Number of Participants  
[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  
Number of Participants with the Indicated Hormone Receptor Status [2]
[units: participants]
 		     
ER+ and/or PgR+ or Unknown     111     113     224  
ER- and PgR-     111     109     220  
Number of Participants with the Indicated Stage of Disease at Initial Diagnosis [3]
[units: participants]
 		     
Stage I to II     107     119     226  
Stage III     75     68     143  
Stage IV     30     24     54  
Unknown     10     11     21  
Number of Participants with the Indicated Eastern Cooperative Oncology Group Performance Status [4]
[units: participants]
 		     
0, Fully Active     103     113     216  
1, Ambulatory, Restricted Strenuous Activity     119     109     228  
Number of Participants with the Indicated Number of Metastatic Sites [5]
[units: participants]
 		     
Greater than or equal to 3     131     115     246  
Less than 3     91     107     198  
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 [6]
[units: months]
Mean ± Standard Deviation 		  27.51  ± 27.481     29.04  ± 34.522     28.27  ± 31.174  
[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.
[2] 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.
[3] 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.
[4] 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.
[5] 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.
[6] 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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2.  Secondary:   Progression-free Survival   [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ]
  Show Outcome Measure 2

3.  Secondary:   Overall Response (OR)   [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ]
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4.  Secondary:   Clinical Benefit   [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ]
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5.  Secondary:   Duration of Response   [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ]
  Show Outcome Measure 5

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 ]
  Show Outcome Measure 6


  Serious Adverse Events
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  Other Adverse Events
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Time Frame No text entered.
Additional Description Serious adverse events and adverse events were collected in the Safety Population, comprised of all randomized participants who received at least one dose of investigational product.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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. This is not a comparative treatment arm.

Other Adverse Events
    Lapatinib Plus Paclitaxel     Placebo Plus Paclitaxel     Lapatinib 1500 mg  
Total, other (not including serious) adverse events        
# participants affected / at risk     219/222     206/221     132/149  
Blood and lymphatic system disorders        
Neutropenia † 1      
# participants affected / at risk     168/222 (75.68%)     103/221 (46.61%)     8/149 (5.37%)  
Leukopenia † 1      
# participants affected / at risk     113/222 (50.90%)     74/221 (33.48%)     10/149 (6.71%)  
Anemia † 1      
# participants affected / at risk     50/222 (22.52%)     22/221 (9.95%)     0/149 (0.00%)  
Granulocytopenia † 1      
# participants affected / at risk     17/222 (7.66%)     15/221 (6.79%)     0/149 (0.00%)  
Gastrointestinal disorders        
Diarrhea † 1      
# participants affected / at risk     171/222 (77.03%)     64/221 (28.96%)     40/149 (26.85%)  
Nausea † 1      
# participants affected / at risk     66/222 (29.73%)     41/221 (18.55%)     0/149 (0.00%)  
Vomiting † 1      
# participants affected / at risk     48/222 (21.62%)     26/221 (11.76%)     0/149 (0.00%)  
Abdominal pain † 1      
# participants affected / at risk     17/222 (7.66%)     10/221 (4.52%)     0/149 (0.00%)  
Constipation † 1      
# participants affected / at risk     8/222 (3.60%)     18/221 (8.14%)     0/149 (0.00%)  
Dyspepsia † 1      
# participants affected / at risk     11/222 (4.95%)     8/221 (3.62%)     0/149 (0.00%)  
Mouth ulceration † 1      
# participants affected / at risk     16/222 (7.21%)     0/221 (0.00%)     0/149 (0.00%)  
Abdominal pain upper † 1      
# participants affected / at risk     13/222 (5.86%)     2/221 (0.90%)     0/149 (0.00%)  
Abdominal distension † 1      
# participants affected / at risk     12/222 (5.41%)     3/221 (1.36%)     0/149 (0.00%)  
General disorders        
Fatigue † 1      
# participants affected / at risk     47/222 (21.17%)     35/221 (15.84%)     0/149 (0.00%)  
Pyrexia † 1      
# participants affected / at risk     29/222 (13.06%)     30/221 (13.57%)     0/149 (0.00%)  
Oedema † 1      
# participants affected / at risk     8/222 (3.60%)     16/221 (7.24%)     8/149 (5.37%)  
Asthenia † 1      
# participants affected / at risk     15/222 (6.76%)     6/221 (2.71%)     0/149 (0.00%)  
Mucosal inflammation † 1      
# participants affected / at risk     18/222 (8.11%)     3/221 (1.36%)     0/149 (0.00%)  
Hepatobiliary disorders        
Hepatic function abnormal † 1      
# participants affected / at risk     17/222 (7.66%)     9/221 (4.07%)     0/149 (0.00%)  
Hyperbilirubinemia † 1      
# participants affected / at risk     12/222 (5.41%)     2/221 (0.90%)     0/149 (0.00%)  
Infections and infestations        
Upper respiratory tract infection † 1      
# participants affected / at risk     20/222 (9.01%)     12/221 (5.43%)     0/149 (0.00%)  
Nasopharyngitis † 1      
# participants affected / at risk     11/222 (4.95%)     11/221 (4.98%)     0/149 (0.00%)  
Pharyngitis † 1      
# participants affected / at risk     9/222 (4.05%)     11/221 (4.98%)     0/149 (0.00%)  
Paronychia † 1      
# participants affected / at risk     17/222 (7.66%)     1/221 (0.45%)     0/149 (0.00%)  
Investigations        
Alanine aminotransferase increased † 1      
# participants affected / at risk     24/222 (10.81%)     17/221 (7.69%)     9/149 (6.04%)  
Aspartate aminotransferase increased † 1      
# participants affected / at risk     19/222 (8.56%)     16/221 (7.24%)     8/149 (5.37%)  
Hemoglobin decreased † 1      
# participants affected / at risk     22/222 (9.91%)     4/221 (1.81%)     0/149 (0.00%)  
Blood alkaline phosphatase increased † 1      
# participants affected / at risk     11/222 (4.95%)     10/221 (4.52%)     0/149 (0.00%)  
White blood cell decreased † 1      
# participants affected / at risk     10/222 (4.50%)     10/221 (4.52%)     0/149 (0.00%)  
Metabolism and nutrition disorders        
Decreased Appetite † 1      
# participants affected / at risk     70/222 (31.53%)     41/221 (18.55%)     0/149 (0.00%)  
Musculoskeletal and connective tissue disorders        
Myalgia † 1      
# participants affected / at risk     30/222 (13.51%)     23/221 (10.41%)     0/149 (0.00%)  
Arthralgia † 1      
# participants affected / at risk     18/222 (8.11%)     14/221 (6.33%)     0/149 (0.00%)  
Musculoskeletal pain † 1      
# participants affected / at risk     10/222 (4.50%)     6/221 (2.71%)     0/149 (0.00%)  
Nervous system disorders        
Neuropathy peripheral † 1      
# participants affected / at risk     30/222 (13.51%)     30/221 (13.57%)     15/149 (10.07%)  
Hypoaesthesia † 1      
# participants affected / at risk     18/222 (8.11%)     25/221 (11.31%)     16/149 (10.74%)  
Headache † 1      
# participants affected / at risk     20/222 (9.01%)     20/221 (9.05%)     0/149 (0.00%)  
Dizziness † 1      
# participants affected / at risk     19/222 (8.56%)     10/221 (4.52%)     0/149 (0.00%)  
Peripheral sensory neuropathy † 1      
# participants affected / at risk     12/222 (5.41%)     12/221 (5.43%)     0/149 (0.00%)  
Psychiatric disorders        
Insomnia † 1      
# participants affected / at risk     12/222 (5.41%)     17/221 (7.69%)     0/149 (0.00%)  
Respiratory, thoracic and mediastinal disorders        
Cough † 1      
# participants affected / at risk     22/222 (9.91%)     19/221 (8.60%)     0/149 (0.00%)  
Dyspnea † 1      
# participants affected / at risk     13/222 (5.86%)     12/221 (5.43%)     0/149 (0.00%)  
Skin and subcutaneous tissue disorders        
Alopecia † 1      
# participants affected / at risk     102/222 (45.95%)     113/221 (51.13%)     61/149 (40.94%)  
Rash † 1      
# participants affected / at risk     130/222 (58.56%)     52/221 (23.53%)     58/149 (38.93%)  
Nail disorder † 1      
# participants affected / at risk     25/222 (11.26%)     3/221 (1.36%)     10/149 (6.71%)  
Pruritus † 1      
# participants affected / at risk     21/222 (9.46%)     6/221 (2.71%)     8/149 (5.37%)  
Dry skin † 1      
# participants affected / at risk     15/222 (6.76%)     3/221 (1.36%)     0/149 (0.00%)  
† Events were collected by systematic assessment
1 Term from vocabulary, MedDRA



  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.


Limitations and Caveats
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.  


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


No publications provided


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00281658     History of Changes
Other Study ID Numbers: EGF104535
Study First Received: January 23, 2006
Results First Received: May 5, 2011
Last Updated: January 24, 2013
Health Authority: Ukraine: Central Ethics Committee;
Brazil: Institutional Review Board
Peru: Institutional Review Board
Norway: Statens Legemiddelverk
Russia: Russian Ministry of Health
Thailand: Ministry of Public Health
Hong Kong: Department of Health
China: Food and Drug Administration
United States: Food and Drug Administration