Pazopanib In Combination With Lapatinib In Adult Patients With Relapsed Malignant Glioma (VEG102857)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00350727
First received: July 10, 2006
Last updated: April 11, 2013
Last verified: May 2012
Results First Received: December 26, 2010  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Glioma
Interventions: Drug: pazopanib
Drug: 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
Phase I and Phase II had two separate participant populations. Enrollment in Phase II was not dependent on the number of participants completing Phase I.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg Starting dose of oral pazopanib of 200 milligrams (mg) once daily (OD) and oral lapatinib 1500 mg OD. The dose of pazopanib (200-800 mg) and lapatinib (500-1500 mg) in cohorts enrolled subsequent to the first dose cohort was determined by the toxicity profile of the combination therapy and the pharmacokinetic results from the prior cohort.
Phase II: Biomarker Positive All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
Phase II: Biomarker Negative All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.

Participant Flow for 2 periods

Period 1:   Phase I: Dose Escalation
    Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg     Phase II: Biomarker Positive     Phase II: Biomarker Negative  
STARTED     34     0     0  
COMPLETED     0     0     0  
NOT COMPLETED     34     0     0  
Adverse Event                 4                 0                 0  
Lack of Efficacy                 25                 0                 0  
Death                 1                 0                 0  
Physician Decision                 1                 0                 0  
Transition to Extension Phase                 3                 0                 0  

Period 2:   Phase II
    Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg     Phase II: Biomarker Positive     Phase II: Biomarker Negative  
STARTED     0     19     22  
COMPLETED     0     0     0  
NOT COMPLETED     0     19     22  
Disease Progression                 0                 15                 16  
Clinical Deterioration                 0                 1                 0  
Withdrawal by Subject                 0                 2                 1  
Adverse Event                 0                 1                 1  
Death                 0                 0                 2  
Sponsor Terminated Study                 0                 0                 1  
Enrolled in Rollover Study                 0                 0                 1  



  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
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg Starting dose of oral pazopanib of 200 milligrams (mg) once daily (OD) and oral lapatinib 1500 mg OD. The dose of pazopanib (200-800 mg) and lapatinib (500-1500 mg) in cohorts enrolled subsequent to the first dose cohort was determined by the toxicity profile of the combination therapy and the pharmacokinetic results from the prior cohort.
Phase II: Biomarker Positive All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN).
Phase II: Biomarker Negative All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN.
Total Total of all reporting groups

Baseline Measures
    Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg     Phase II: Biomarker Positive     Phase II: Biomarker Negative     Total  
Number of Participants  
[units: participants]
  34     19     22     75  
Age, Customized [1]
[units: participants]
       
20-29 years old     1     0     2     3  
30-39 years old     8     0     3     11  
40-49 years old     11     6     6     23  
50-59 years old     10     5     8     23  
60-69 years old     3     7     2     12  
>=70 years old     1     1     1     3  
Gender  
[units: participants]
       
Female     11     5     5     21  
Male     23     14     17     54  
Race/Ethnicity, Customized  
[units: participants]
       
African American/African Heritage     0     0     1     1  
White/Caucasian/European Heritage     34     19     21     74  
[1] Number of participants falling into the indicated age groups.



  Outcome Measures
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1.  Primary:   Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure   [ Time Frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II) ]

2.  Primary:   Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure   [ Time Frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II) ]

3.  Primary:   Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate   [ Time Frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II) ]

4.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for Albumin   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

5.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

6.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

7.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

8.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

9.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine)   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

10.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroid Stimulating Hormone   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

11.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for Total T3   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

12.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for Hemoglobin   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

13.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for Hematocrit   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

14.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

15.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for International Normalized Ratio (Prothrombin Time)   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

16.  Primary:   Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time   [ Time Frame: Baseline to study completion (up to 878 days for Phase II) ]

17.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

18.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

19.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

20.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

21.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

22.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

23.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for Free T3 (Triiodothyronine)   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

24.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

25.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for Total T3   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

26.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

27.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

28.  Primary:   Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

29.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time)   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

30.  Primary:   Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time   [ Time Frame: Baseline to study completion (up to 844 days for Phase I) ]

31.  Primary:   Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose   [ Time Frame: Cycle 1 in Phase I (up to Day 28) ]

32.  Primary:   Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation   [ Time Frame: Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878) ]

33.  Primary:   Overall Response (OR) in Phase II Based on the Investigator-assigned Response   [ Time Frame: Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878) ]

34.  Primary:   Overall Response (OR) in Phase II Based on an Independent Radiologist's Review   [ Time Frame: Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878) ]

35.  Primary:   Progression-free Survival at 6 Months   [ Time Frame: Date of the first dose of study drug to 6 months ]

36.  Secondary:   Progression-free Survival   [ Time Frame: Date of the first dose of study drug to the date of documented and confirmed progression by Mac Donald criteria, or to date of death due to any cause (up to Day 878) ]

37.  Secondary:   Time to Disease Progression or Death Due to Any Cause   [ Time Frame: Date of the first dose of study drug to the date of documented and confirmed progression by Mac Donald criteria, or to date of death due to any cause (up to Day 878) ]

38.  Secondary:   Phase I: Pharmacokinetic Parameters Including AUC(0-24), [AUC(0-12) for Patients on Twice Daily Administration], Cmax, the Time to Maximum Observed Concentration (Tmax) and C24 of Pazopanib and Lapatinib When Administered in Combination With EIAC.   [ Time Frame: Completed during first cycle of treatment. ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

39.  Secondary:   Phase II: Pharmacokinetic Parameters Including AUC(0-24), [AUC(0-12) for Patients on Twice Daily Administration], Cmax, Tmax, and C24 of Pazopanib and Lapatinib, as Appropriate, When Administered Together in Combination With Non-EIAC.   [ Time Frame: Completed during first cycle of treatment. ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

40.  Secondary:   Phase II: Plasma Concentrations of the Circulating Biomarkers VEGF, sVEGFR-1, and sVEGFR-2.   [ Time Frame: Completed during first cycle of treatment. ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No


  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
No text entered.


  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 by GlaxoSmithKline

Publications automatically indexed to this study:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00350727     History of Changes
Obsolete Identifiers: NCT00412711
Other Study ID Numbers: VEG102857
Study First Received: July 10, 2006
Results First Received: December 26, 2010
Last Updated: April 11, 2013
Health Authority: European Union: European Medicines Agency
United States: Food and Drug Administration