This is an open-label, single-center, single-arm, dose escalation and dose expansion Phase I/IIa study designed to determine the recommended Phase 2 dose (RP2D) and the safety and tolerability profile along with preliminary signs of efficacy of rivoceranib in combination with paclitaxel as a second-line therapy in advanced, recurrent and/or metastatic gastric or gastroesophageal junction cancer. This study will also characterize the pharmacokinetic (PK) parameters of rivoceranib and paclitaxel when given in combination.
Primary Phase I Objectives * To determine the RP2D dose of rivoceranib in combination with paclitaxel. Primary Phase II Objectives * To determine clinical activity of the combination of rivoceranib and paclitaxel. Secondary Phase I Objectives * To evaluate the PK of rivoceranib and paclitaxel when given in combination. * To assess the efficacy of rivoceranib in combination with paclitaxel. Secondary Phase II Objectives * To assess the efficacy of rivoceranib in combination with paclitaxel. * To assess the safety and tolerability of rivoceranib in combination with paclitaxel. * To assess the PK of rivoceranib and paclitaxel when given in combination.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Film-coated tablet
Solution administered intravenously
Asan Medical Center
Seoul, South Korea
Phase I: Incidence of Dose-Limiting Toxicities (DLT) During Cycle 1
The number and proportion of participants experiencing DLTs will be reported by dose level, based on DLT observations during Cycle 1. Each Cycle is 28 days.
Time frame: Cycle 1 (first 28 days)
Phase I: Number of Participants Reporting Adverse Events (AEs) and Serious AEs (SAEs)
An AE is any untoward medical occurrence in a participant or participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, or important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent 1 of the other outcomes listed above.
Time frame: Up to 24 months
Phase II: Objective Response Rate (ORR)
ORR is the percentage of participants who achieve objective tumor response (complete response \[CR\] or partial response \[PR\]) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria for response.
Time frame: Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months
Phase I: Maximum Observed Concentration (Cmax)
Time frame: Day 1 & 15 of Cycle 1 (each cycle is 28 days)
Phase I: Time to Maximum Observed Concentration (tmax)
Time frame: Day 1 & 15 of Cycle 1 (each cycle is 28 days)
Phase I: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC0-t)
Time frame: Day 1 & 15 of Cycle 1 (each cycle is 28 days)
Phase I: Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-∞)
Time frame: Day 1 & 15 of Cycle 1 (each cycle is 28 days)
Phase I: Terminal Half-life (t1/2)
Time frame: Day 1 & 15 of Cycle 1 (each cycle is 28 days)
Phase I: Apparent Oral Plasma Clearance (CL/F)
Time frame: Day 1 & 15 of Cycle 1 (each cycle is 28 days)
Phase I: Apparent Volume of Distribution (Vz/F)
Time frame: Day 1 & 15 of Cycle 1 (each cycle is 28 days)
Phase I: Terminal Rate Constant (λz)
Time frame: Day 1 & 15 of Cycle 1 (each cycle is 28 days)
Phase I: ORR
ORR by RECIST 1.1
Time frame: Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months
Phase I: Progression-free Survival (PFS)
Defined as time from first dose of study drug (Cycle 1 Day 1) to the time of first documented disease progression or death due to any cause.
Time frame: Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months
Phase I: Overall survival (OS)
OS is the time from first dose of study drug (Cycle 1 Day 1) to the time of death from any cause.
Time frame: Ongoing assessment from enrollment until end of study, up to approximately 24 months
Phase I: Disease Control Rate (DCR)
DCR is defined as the percentage of participants who achieve CR or PR and stable disease (SD) at ≥12 weeks.
Time frame: Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months
Phase I: Duration of Response
Defined as the time from first documentation of (complete response or partial response) to the first documentation of progression.
Time frame: Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months
Phase II: PFS
Defined as time from first dose of study drug (Cycle 1 Day 1) to the time of first documented disease progression or death due to any cause.
Time frame: Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months
Phase II: OS
OS is the time from first dose of study drug (Cycle 1 Day 1) to the time of death from any cause.
Time frame: Ongoing assessment from enrollment until end of study, up to approximately 24 months
Phase II: DCR
DCR is defined as the percentage of participants who achieve CR or PR and SD at ≥12 weeks.
Time frame: Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months
Phase II: Duration of Response
Defined as the time from first documentation of (complete response or partial response) to the first documentation of progression.
Time frame: Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months
Phase II: Number of Participants With AEs and SAEs
Adverse Events and Serious Adverse Events
Time frame: Ongoing assessment from enrollment until end of study, approximately 24 months
Phase II: Concentration at the End of the Dosage Interval (Ctrough)
Ctrough is characterized at steady state after single and multiple cycles of treatment.
Time frame: Ongoing assessment from enrollment until end of study, approximately 24 months
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