Pazopanib In Combination With Lapatinib In Adult Patients With Relapsed Malignant Glioma
- Registration Number
- NCT00350727
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This study is being conducted to characterize the safety/tolerability of pazopanib and lapatinib when administered in combination with enzyme-inducing anticonvulsants in patients with recurrent Grade III or IV malignant gliomas.
- Detailed Description
This study is being conducted to characterize the safety/tolerability of pazopanib and lapatinib when administered in combination with enzyme-inducing anticonvulsants in patients with recurrent Grade III or IV malignant gliomas.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 75
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Combination lapatinib Pazopanib and Lapatinib in combination. Subjects remain on treatment until disease progression or withdrawal from study. Combination pazopanib Pazopanib and Lapatinib in combination. Subjects remain on treatment until disease progression or withdrawal from study.
- Primary Outcome Measures
Name Time Method Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroid Stimulating Hormone Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. mmHg, millimeters of mercury.
Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. bpm, beats per minute.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Total T3 Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Free T3 (Triiodothyronine) Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. mmHg, millimeters of mercury.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Albumin Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time) Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Prothrombin time is a measure of the extrinsic pathway of coagulation that is used to determine the clotting tendency of blood. The International Normalized Ratio is the ratio of a patient's prothrombin time to a normal (control) sample.
Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose Cycle 1 in Phase I (up to Day 28) A dose-limiting toxicity (DLT) is defined as predefined adverse events or events that prevented participants from receiving 75% of their scheduled doses or from starting their next treatment period. The dose at which no more than 1 out of 6 participants experiences a DLT is defined as the optimally tolerated regimen. The OTR is important because it determines the highest dose combination that can be given without significant toxicity.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Overall Response (OR) in Phase II Based on an Independent Radiologist's Review 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) OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by \>=50%, respectively, on consecutive scans \[CS\] \>=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of \>=25% on CS \>=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as \<8 w.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine) Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Hematocrit Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. The hematocrit is the proportion of blood volume that is occupied by red blood cells.
Mean Change From Baseline to Maximum Value in Phase II of the Study for International Normalized Ratio (Prothrombin Time) Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Prothrombin time is a measure of the extrinsic pathway of coagulation that is used to determine the clotting tendency of blood. The International Normalized Ratio is the ratio of a patient's prothrombin time to a normal (control) sample.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Partial thromboplastin time is a performance indicator detecting abnormalities in blood clotting.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Overall Response (OR) in Phase II Based on the Investigator-assigned Response 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) OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by \>=50%, respectively, on consecutive scans \[CS\] \>=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of \>=25% on CS \>=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as \<8 w.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Hemoglobin Baseline to study completion (up to 878 days for Phase II) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Total T3 Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. The hematocrit is the proportion of blood volume that is occupied by red blood cells.
Progression-free Survival at 6 Months Date of the first dose of study drug to 6 months Progression-free survival (PFS) analysis was performed on all participants. PFS is presented as the number of participants experiencing disease progression or death due to any cause. Participants who are alive and have not progressed at the time of analysis are considered censored, and the date associated with the last visit with disease assessment will be used. The participants who are still alive and whose follow-up extends to at least 6 months are considered At Risk.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time Baseline to study completion (up to 844 days for Phase I) Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Partial thromboplastin time is a performance indicator detecting abnormalities in blood clotting.
Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation 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) OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by \>=50%, respectively, on consecutive scans \[CS\] \>=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of \>=25% on CS \>=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as \<8 w.
- Secondary Outcome Measures
Name Time Method 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. Completed during first cycle of treatment. Phase II: Plasma Concentrations of the Circulating Biomarkers VEGF, sVEGFR-1, and sVEGFR-2. Completed during first cycle of treatment. Progression-free Survival 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) Progression-free survival (PFS) analysis was performed on all participants. PFS is presented as the number of participants experiencing disease progression or death due to any cause. Participants who are alive and have not progressed at the time of analysis are considered censored, and the date associated with the last visit with disease assessment will be used.
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. Completed during first cycle of treatment. Time to Disease Progression or Death Due to Any Cause 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)