A Study to Evaluate Safety, Tolerability, and Efficacy Profile of Rivoceranib With Paclitaxel in Advanced Gastric or Gastroesophageal Junction Cancer
- Conditions
- Gastric CancerGastroesophageal Junction Adenocarcinoma
- Interventions
- Registration Number
- NCT03707028
- Lead Sponsor
- Elevar Therapeutics
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 12
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rivoceranib with Paclitaxel Rivoceranib Participants will receive oral daily doses of rivoceranib per 28-day cycle (as its mesylate salt) with a fixed dose of paclitaxel given intravenously on Day 1, Day 8, and Day 15 of the 28-day cycle. Rivoceranib with Paclitaxel Paclitaxel Participants will receive oral daily doses of rivoceranib per 28-day cycle (as its mesylate salt) with a fixed dose of paclitaxel given intravenously on Day 1, Day 8, and Day 15 of the 28-day cycle.
- Primary Outcome Measures
Name Time Method Phase I: Incidence of Dose-Limiting Toxicities (DLT) During Cycle 1 Cycle 1 (first 28 days) 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.
Phase I: Number of Participants Reporting Adverse Events (AEs) and Serious AEs (SAEs) Up to 24 months 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.
Phase II: Objective Response Rate (ORR) Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months 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.
- Secondary Outcome Measures
Name Time Method Phase I: Time to Maximum Observed Concentration (tmax) 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) Day 1 & 15 of Cycle 1 (each cycle is 28 days) Phase I: Maximum Observed Concentration (Cmax) 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-∞) Day 1 & 15 of Cycle 1 (each cycle is 28 days) Phase I: Terminal Half-life (t1/2) Day 1 & 15 of Cycle 1 (each cycle is 28 days) Phase I: Apparent Oral Plasma Clearance (CL/F) Day 1 & 15 of Cycle 1 (each cycle is 28 days) Phase I: Apparent Volume of Distribution (Vz/F) Day 1 & 15 of Cycle 1 (each cycle is 28 days) Phase I: ORR Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months ORR by RECIST 1.1
Phase I: Terminal Rate Constant (λz) Day 1 & 15 of Cycle 1 (each cycle is 28 days) Phase I: Progression-free Survival (PFS) Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months 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.
Phase I: Overall survival (OS) Ongoing assessment from enrollment until end of study, up to approximately 24 months OS is the time from first dose of study drug (Cycle 1 Day 1) to the time of death from any cause.
Phase I: Disease Control Rate (DCR) Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months DCR is defined as the percentage of participants who achieve CR or PR and stable disease (SD) at ≥12 weeks.
Phase I: Duration of Response Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months Defined as the time from first documentation of (complete response or partial response) to the first documentation of progression.
Phase II: PFS Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months 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.
Phase II: OS Ongoing assessment from enrollment until end of study, up to approximately 24 months OS is the time from first dose of study drug (Cycle 1 Day 1) to the time of death from any cause.
Phase II: DCR Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months DCR is defined as the percentage of participants who achieve CR or PR and SD at ≥12 weeks.
Phase II: Duration of Response Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months Defined as the time from first documentation of (complete response or partial response) to the first documentation of progression.
Phase II: Number of Participants With AEs and SAEs Ongoing assessment from enrollment until end of study, approximately 24 months Adverse Events and Serious Adverse Events
Phase II: Concentration at the End of the Dosage Interval (Ctrough) Ongoing assessment from enrollment until end of study, approximately 24 months Ctrough is characterized at steady state after single and multiple cycles of treatment.
Trial Locations
- Locations (1)
Asan Medical Center
🇰🇷Seoul, Korea, Republic of