Randomized, Double-blind Phase 2 Study Of Axitinib (Ag-013736) With Or Without Dose Titration In Patients With Metastatic Renal Cell Carcinoma

简要总结

主要结局

次要结局

• Progression-Free Survival (PFS)(Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks.)
• Overall Survival (OS)(Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks.)
• Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib,(C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose)
• Duration of Response (DR)(Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks)
• Maximum Observed Plasma Concentration (Cmax) of Axitinib(Cycle 2 Day 15 (C2D15): pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose)
• Apparent Oral Clearance (CL/F) of Axitinib(C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose)
• Change From Baseline in Diastolic Blood Pressure(At screening (D-14 to D-1); lead-in period: Cycle 1 - Day 1 and Day 15; Cycle 2 - Day 1 and Day 15; Cycle 3 & subsequent cycles Day 1; end of study and follow-up 28 days after last dose.)
• Comparison of Circulating Endothelial Cells (CECs) in Blood: Cluster of Differentiation (CD)146+/CD105+ at Baseline(At baseline - Beginning of the lead-in period (Cycle 1 Day 1))
• PFS in Subgroups That Were Defined by Vascular Endothelial Growth Factor A (VEGFA) or Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Polymorphisms(At baseline - Beginning of the lead-in period (Cycle 1 Day 1))
• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Axitinib(C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose)
• Apparent Volume of Distribution During the Elimination Phase (Vz/F) for Axitinib(C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose)
• Change From Baseline in Systolic Blood Pressure(At screening (D-14 to D-1); lead-in period: Cycle 1 - Day 1 and Day 15; Cycle 2 - Day 1 and Day 15; Cycle 3 & subsequent cycles Day 1; end of study and follow-up 28 days after last dose.)
• Comparison of the Ratio of CECs in Blood: CD146+/CD105+ at Each Time Point to Baseline(At end of the lead-in period (Cycle 1 Day 15), Cycle 2 Day 15 and End of therapy (EOT))
• Circulating Endothelial Cells (CECs) in Blood: CD31+/CD146+(At baseline - Beginning of the lead-in period (Cycle 1 Day 1))
• Comparison of Ratio of CECs in Blood: CD31+/CD146+ at Each Time Point to Baseline(At end of the lead-in period (Cycle 1 Day 15), Cycle 2 Day 15 and End of therapy (EOT))
• Area Under the Curve From Time Zero to 24 Hours[AUC(0-24)] for Axitinib(C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose)
• Plasma Decay Half-Life (t1/2) for Axitinib(C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose)
• ORR in Subgroups That Were Defined by Vascular Endothelial Growth Factor A (VEGFA) or Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Polymorphisms(At baseline - Beginning of the lead-in period (Cycle 1 Day 1))