A Phase 1 Study of AMG 211 in Participants with Advanced Gastrointestinal CancerN/A
Study Details
The purpose of this Phase 1 study is to determine if AMG 211 given as a continous intravenous (IV) infusion is safe and tolerable in adult participants that have advanced gastrointestinal adenocarcinoma. The study will be conducted in multiple sites and test increasing doses of AMG 211. The safety of participants will be monitored by intensive assessment of vital signs, electrocardiograms, physical examinations, and laboratory tests. Efficacy will be assessed by the usual imaging procedures and their interpretation.
Protocol Summary
Number of Participants with Dose-Limiting Toxicities (DLTs)
Timeframe: 28 days
Number of Participants with Adverse Events
Timeframe: From first dose of AMG 211 until 4 weeks after the last dose. The median time frame was 79 days.
Maximum Observed Concentration (Cmax) of AMG 211 in Cycle 1 in Participants who Received Dosing for 7 or 14 Days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Maximum Observed Concentration (Cmax) of AMG 211 in Cycle 1 in Participants Who Received Dosing for 28 Days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Area Under the Serum Concentration-Time Curve (AUC) from Time 0 to the Last Quantifiable Concentration in Participants Who Received Dosing for 7 or 14 Days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Area Under the Serum Concentration-Time Curve (AUC) from Time 0 to the Last Quantifiable Concentration in Participants Who Received Dosing for 28 Days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Area Under the Serum Concentration-Time Curve from Time 0 to Infinity (AUCinf) in Participants Who Received Dosing for 7 or 14 Days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Area Under the Serum Concentration-Time Curve from Time 0 to Infinity (AUCinf) in Participants Who Received Dosing for 28 days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Terminal half-life (T1/2) of AMG-211 in Participants Who Received Dosing for 7 or 14 days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Terminal Half-life of AMG-211 in Participants Who Received Dosing for 28 days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Concentration of AMG 211 at Steady State (Css) in Participants Who Received Dosing for 7 or 14 days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion
Concentration of AMG 211 at Steady State (Css) in Participants Who Received Dosing for 28 days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Serum Clearance of AMG 211 in Participants Who Received Dosing for 7 or 14 days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Serum Clearance of AMG 211 in Participants Who Received Dosing for 28 days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Volume of Distribution at Steady-state (Vss) in Participants Who Received Dosing for 7 or 14 days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Volume of Distribution at Steady-state (Vss) in Participants Who Received Dosing for 28 days
Timeframe: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Number of Participants with Anti-AMG 211 Antibody Formation
Timeframe: Predose and 24 hours after the end of infusion during each treatment cycle, until 4 weeks after the last dose. The median time frame was 79 days.
Number of Participants with an Overall Objective Response
Timeframe: Disease response was assessed every second cycle (8-10 weeks) until 4 weeks after the last dose. The median time frame was 79 days.
Duration of Response
Timeframe: Disease response was assessed every second cycle (8-10 weeks) until 4 weeks after the last dose. The median time frame was 79 days.
Time to Response
Timeframe: Disease response was assessed every second cycle (8-10 weeks) until 4 weeks after the last dose. The median time frame was 79 days.
Time to Tumor Progression in Participants Treated at the MTD
Timeframe: From first dose of AMG 211 until tumor progression, assessed through the end of study (up to 4 weeks after the last dose). The median time frame was 79 days.
Progression Free Survival (PFS) at 6 Months in Participants Treated at the MTD
Timeframe: 6 months