Lapatinib in Combination With Weekly Paclitaxel in Patients With ErbB2 Amplified Advanced Gastric Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00486954
First received: June 13, 2007
Last updated: June 12, 2013
Last verified: January 2013
Results First Received: December 20, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Neoplasms, Gastrointestinal Tract
Interventions: Drug: Lapatinib
Drug: Paclitaxel

  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
This study consisted of a Pilot part and a Randomized part. The Pilot part and the Randomized part had two separate participant (par.) populations. The study period of the Randomized part was from 31 March 2008 to 5 January 2012 (cut-off date for efficacy). Follow-up was conducted until 30 October 2012 (cut-off date for safety analysis).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In the Pilot part, par. were enrolled in this study based on their gastrectomy status: non-gastrectomy (intact stomach), partial gastrectomy (gastrectomy with pylorus preserved), and gastrectomy (pylorus removed). However, no par. with partial gastrectomy were enrolled. In the Randomized part, par. were randomized to two treatment arms.

Reporting Groups
  Description
Lapatinib Plus Paclitaxel in Non-gastrectomy Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m^2).
Lapatinib Plus Paclitaxel in Partial Gastrectomy Participants Participants with partial gastrectomy (which includes preservation of the pylorus) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m^2. Partial gastrectomy (pylorus preserved) is very rare population in Japan. As a result, no such participants were recruited into this cohort.
Lapatinib Plus Paclitaxel in Gastrectomy Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m^2.
Lapatinib Plus Paclitaxel Participants received 1500 mg of oral lapatinib once daily throughout the study duration. Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m^2 (on Days 1, 8, and 15 of each cycle).
Paclitaxel Alone Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m^2 (on Days 1, 8, and 15 of each cycle).

Participant Flow for 2 periods

Period 1:   Pilot Part
    Lapatinib Plus Paclitaxel in Non-gastrectomy Participants     Lapatinib Plus Paclitaxel in Partial Gastrectomy Participants     Lapatinib Plus Paclitaxel in Gastrectomy Participants     Lapatinib Plus Paclitaxel     Paclitaxel Alone  
STARTED     6     0     6     0     0  
COMPLETED     0     0     0     0     0  
NOT COMPLETED     6     0     6     0     0  
Adverse Event                 4                 0                 5                 0                 0  
Disease Progression                 2                 0                 1                 0                 0  

Period 2:   Randomized Part
    Lapatinib Plus Paclitaxel in Non-gastrectomy Participants     Lapatinib Plus Paclitaxel in Partial Gastrectomy Participants     Lapatinib Plus Paclitaxel in Gastrectomy Participants     Lapatinib Plus Paclitaxel     Paclitaxel Alone  
STARTED     0     0     0     132     129  
COMPLETED     0     0     0     112     115  
NOT COMPLETED     0     0     0     20     14  
Lost to Follow-up                 0                 0                 0                 0                 1  
Withdrawal by Subject                 0                 0                 0                 1                 0  
Sponsor Terminated Study                 0                 0                 0                 19                 13  



  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 in Non-gastrectomy Participants In the Pilot part, participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m^2).
Lapatinib Plus Paclitaxel in Gastrectomy Participants In the Pilot part, participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m^2.
Lapatinib Plus Paclitaxel in Randomized Part Participants received 1500 mg of oral lapatinib once daily throughout the study duration. Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m^2 (on Days 1, 8, and 15 of each cycle).
Paclitaxel Alone in Randomized Part Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m^2 (on Days 1, 8, and 15 of each cycle).
Total Total of all reporting groups

Baseline Measures
    Lapatinib Plus Paclitaxel in Non-gastrectomy Participants     Lapatinib Plus Paclitaxel in Gastrectomy Participants     Lapatinib Plus Paclitaxel in Randomized Part     Paclitaxel Alone in Randomized Part     Total  
Number of Participants  
[units: participants]
  6     6     132     129     273  
Age  
[units: Years]
Mean ± Standard Deviation
  57.5  ± 11.31     57.2  ± 10.98     60.8  ± 9.45     60.4  ± 10.96     60.5  ± 10.23  
Gender  
[units: Participants]
         
Female     1     0     31     23     55  
Male     5     6     101     106     218  
Race/Ethnicity, Customized  
[units: Participants]
         
Asian - Japanese Heritage     6     6     52     48     112  
Asian - East Asian Heritage     0     0     73     75     148  
Asian - South East Asian Heritage     0     0     7     6     13  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Dose Limiting Toxicities (DLTs) in the Pilot Part of the Study   [ Time Frame: 28 days ]

2.  Primary:   Overall Survival (OS) in the Randomized Part of the Study   [ Time Frame: From randomization until death due to any cause (up to 42.58 months) ]

3.  Secondary:   Maximum Plasma Concentration (Cmax) of Lapatinib in the Pilot Part of the Study   [ Time Frame: Days 8 and 14 ]

4.  Secondary:   Time to Cmax (Tmax) of Lapatinib in the Pilot Part of the Study   [ Time Frame: Days 8 and 14 ]

5.  Secondary:   Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lapatinib in the Pilot Part of the Study   [ Time Frame: Days 8 and 14 ]

6.  Secondary:   Cmax of Paclitaxel in the Pilot Part of the Study   [ Time Frame: Days 1 and 8 ]

7.  Secondary:   Tmax of Paclitaxel in the Pilot Part of the Study   [ Time Frame: Days 1 and 8 ]

8.  Secondary:   AUC(0-24) of Paclitaxel in the Pilot Part of the Study   [ Time Frame: Days 1 and 8 ]

9.  Secondary:   Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Paclitaxel in the Pilot Part of the Study   [ Time Frame: Days 1 and 8 ]

10.  Secondary:   Half-life of Paclitaxel in the Pilot Part of the Study   [ Time Frame: Days 1 and 8 ]

11.  Secondary:   Clearance of Paclitaxel in the Pilot Part of the Study   [ Time Frame: Days 1 and 8 ]

12.  Secondary:   Distribution Volume at Steady State (Vss) of Paclitaxel in the Pilot Part of the Study   [ Time Frame: Days 1 and 8 ]

13.  Secondary:   Progression-free Survival (PFS) in the Randomized Part of the Study   [ Time Frame: From randomization until disease progression or death due to any cause (up to 42.35 months) ]

14.  Secondary:   Time to Progression in the Randomized Part of the Study   [ Time Frame: From randomization until disease progression or death due to disease (up to 42.35 months ) ]

15.  Secondary:   Percentage of Participants With Overall Response in the Randomized Part of the Study   [ Time Frame: From randomization up to 5.62 months ]

16.  Secondary:   Number of Participants With the Indicated Time to Response in the Randomized Part of the Study   [ Time Frame: up to 5.62 months ]

17.  Secondary:   Duration of Response in the Randomized Part of the Study   [ Time Frame: up to 18.27 months ]

18.  Secondary:   Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study   [ Time Frame: From the first dose of investigational product to 30 days after the last dose (up to 110.3 weeks in the Randomized part) ]

19.  Secondary:   Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire (EORTC QLQ-C30) Global Health Status (GHS)/QOL Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

20.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Physical Functioning Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

21.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Role Functioning Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

22.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

23.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

24.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Social Functioning Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

25.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Fatigue Symptom Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

26.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Symptom Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

27.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Pain Symptom Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

28.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Dyspnea Symptom Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

29.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Insomnia Symptom Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

30.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Appetite Loss Symptom Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

31.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Constipation Symptom Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

32.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Diarrhea Symptom Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

33.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Symptom Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

34.  Secondary:   Change From Baseline in the EORTC QLQ-STO22 Dysphagia Scale Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

35.  Secondary:   Change From Baseline in the EORTC QLQ-STO22 Pain Scale Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

36.  Secondary:   Change From Baseline in the EORTC QLQ-STO22 Reflux Symptoms Scale Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

37.  Secondary:   Change From Baseline in the EORTC QLQ-STO22 Eating Restrictions Scale Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

38.  Secondary:   Change From Baseline in the EORTC QLQ-STO22 Anxiety Scale Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

39.  Secondary:   Change From Baseline in the EORTC QLQ-STO22 Dry Mouth Scale Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

40.  Secondary:   Change From Baseline in the EORTC QLQ-STO22 Taste Scale Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

41.  Secondary:   Change From Baseline in the EORTC QLQ-STO22 Body Image Scale Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

42.  Secondary:   Change From Baseline in the EORTC QLQ-STO22 Hair Loss Scale Score at the End of Therapy in the Randomized Part of the Study   [ Time Frame: Baseline and end of therapy (up to 42.58 months) ]

43.  Secondary:   Number of Participants With the Indicated Epidermal Growth Factor Receptor (EGFR) Immunohistochemistry Intensity in the Randomized Part of the Study   [ Time Frame: Pretreatment ]

44.  Secondary:   Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study   [ Time Frame: Pretreatment ]

45.  Secondary:   Number of Participants With Mutations That May Correlate With Response and Toxicity to Lapatinib   [ Time Frame: Pretreatment ]


  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


No publications provided


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00486954     History of Changes
Other Study ID Numbers: 104578
Study First Received: June 13, 2007
Results First Received: December 20, 2012
Last Updated: June 12, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare