E7050 in Combination With Cisplatin and Capecitabine Versus Cisplatin and Capecitabine Alone in Patients With Advanced or Metastatic Solid Tumors and Previously Untreated Gastric Cancer
- Conditions
- Advanced or Metastatic Solid TumorsPreviously Untreated Gastric Cancer
- Interventions
- Registration Number
- NCT01355302
- Lead Sponsor
- Eisai Inc.
- Brief Summary
The purpose of this study is to determine the following: 1. Find the maximum tolerated dose of E7050 when given in combination with cisplatin and capecitabine in patients with advance or metastatic solid tumors, and 2) Whether E7050 in combination with cisplatin and capecitabine is more effective in patients with previously untreated gastric cancer versus cisplatin and capecitabine alone.
- Detailed Description
This open-label, multicenter, randomized study will consist of 2 phases:
Phase Ib: a safety run-in period with 3 ascending doses of E7050 in combination with fixed doses of Cisplatin and Capecitabine. This phase will enroll approximately 10 to 15 patients.
* Phase II: a randomized 2-arm design which will enroll 80 patients.
In the phase II portion, Patients will receive study treatment , E7050 in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone) for approximately six 21-day cycles (18 weeks). Beyond 18 weeks, patients who are experiencing clinical benefit may continue E7050, with or without Capecitabine (Arm 1), or may continue Capecitabine alone (Arm 2), depending on the original randomization treatment arm. Patients will continue treatment for as long as clinical benefit is sustained and the treatment is well tolerated, until the occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, or withdrawal by investigator, whichever occurs first. Patients will participate in either phase Ib or phase II.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 7
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase Ib: Cohort 1 and 2 and 3 E7050 Phase Ib: Cohort 1; 200 mg E7050 + 80 mg/m2 cisplatin + 1000 mg/m2 capecitabine Cohort 2; 300 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Cohort 3; 400 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Phase II: Arm 1; E7050 + cisplatin+ capecitabine capecitabine Phase II: Arm 1; MTD E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Phase Ib: Cohort 1 and 2 and 3 cisplatin Phase Ib: Cohort 1; 200 mg E7050 + 80 mg/m2 cisplatin + 1000 mg/m2 capecitabine Cohort 2; 300 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Cohort 3; 400 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Phase II: Arm 1; E7050 + cisplatin+ capecitabine E7050 Phase II: Arm 1; MTD E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Phase II: Arm 1; E7050 + cisplatin+ capecitabine cisplatin Phase II: Arm 1; MTD E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Phase Ib: Cohort 1 and 2 and 3 capecitabine Phase Ib: Cohort 1; 200 mg E7050 + 80 mg/m2 cisplatin + 1000 mg/m2 capecitabine Cohort 2; 300 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Cohort 3; 400 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine
- Primary Outcome Measures
Name Time Method Time to Maximum Concentration (Tmax) of Golvatinib Cycle 1 (Day -2); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), 24, and 48 hours after study treatment. Cycle 2 (Day 1); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), and 24 hours after study treatment. Tmax was defined as the time at which Cmax was observed for golvatinib in combination with cisplatin and capecitabine.
Area Under The Concentration-Time Curve (AUC) From 0 to 24 Hours of Golvatinib Cycle 1 (Day -2); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), 24, and 48 hours after study treatment. Cycle 2 (Day 1); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), and 24 hours after study treatment. On days when pharmacokinetic (PK) samples were to be drawn, a predose blood sample was obtained prior to administration of golvatinib and capecitabine. After administration of study drugs, a second postdose blood sample was taken. The amount of golvatinib in the participant's blood was analyzed and the AUC was calculated. The AUC reflects the actual body exposure to drug after administration of a dose of the drug and is dependent on the rate of elimination of the drug from the body and the dose administered. Predose samples that were below the limit of quantitation (BLQ) or missing were assigned a numerical value of zero for the calculation of AUC. Any other BLQ concentrations were assigned a value of zero. Results were expressed in nanogramsĀ·hour/milliter (ngĀ·h/mL).
Maximum Concentration (Cmax) of Golvatinib Cycle 1 (Day -2); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), 24, and 48 hours after study treatment. Cycle 2 (Day 1); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), and 24 hours after study treatment. Blood samples were drawn to analyze the amount of golvatinib in the participant's serum. Maximum concentration refers to the maximum (or peak) serum concentration of study drug in the participant's system after administration of the study drug and prior to the administration of a second dose of the study drug. Results were expressed in nanograms/milliliter (ng/mL).
Number of Participants With a Treatment-Emergent Adverse Event (TEAE) From date of first dose up to 30 days after the last dose of study treatment, up to approximately 1 year 1 month. Safety assessments consisted of monitoring and recording all adverse events (AEs) and serious AEs; regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); and performance of physical examinations. A TEAE was defined as an adverse event (AE) that had an onset date, or a worsening in severity from Baseline (pretreatment), on or after the first dose of study drug up to 30 days after the date of last study treatment.
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) Until disease progression or death for 3 years The study was terminated prior to enrollment in Phase 2 so this outcome measure was not conducted.
Time to Progression (TTP) Until disease progression or death for 3 years The study was terminated prior to enrollment in Phase 2 so this outcome measure was not conducted.
Trial Locations
- Locations (19)
Boca Raton Clinical Research Associates, Inc
šŗšøPlantation, Florida, United States
Robert H. Lurie Comprenhensive Cancer Center of Northwestern University
šŗšøChicago, Illinois, United States
University of Michigan Comprehensive Cancer Center
šŗšøAnn Arbor, Michigan, United States
Barbara Ann Karmanos Cancer Institute
šŗšøDetroit, Michigan, United States
Duke University Medical Center
šŗšøDurham, North Carolina, United States
University of North Carolina at Chapel Hill
šŗšøChapell Hill, North Carolina, United States
Henry Ford Medical Center
šŗšøDetroit, Michigan, United States
Chelyabinsk Regional Oncology Dispensary
š·šŗChelyabinsk, Russian Federation
Mercy Cancer Centerr at St. Anne
šŗšøToledo, Ohio, United States
SI Dnipropetrovsk Medical Academy of MOHU ch of Oncology and Medical Radiology
šŗš¦Dnipropetrovsk, Ukraine
Municipal Clinical Medical and Prophylactic Institution Donetsk Regional Antitumor Centre
šŗš¦Donetsk, Ukraine
Barts and the London NHS Trust
š¬š§London, Greater London, United Kingdom
Lviv State Oncol. Reg. Treatment and Diagnostic Center
šŗš¦Lviv, Ukraine
Sarah Cannon Research UK
š¬š§London, Greater London, United Kingdom
The Christie NHS Foundation Trust
š¬š§Manchester, Greater Manchester, United Kingdom
Arizona Oncology Associates, PC - CASA
šŗšøTucson, Arizona, United States
GOU VPO St-Petersburg SMA n/a Mechnikov Fed. Agen. of Healthcare and Social Developm.
š·šŗSt Petersburg, Russian Federation
Kyiv City Clinical Oncological Center
šŗš¦Kyiv, Ukraine
FSI "SRC of Oncology n. a. N.N.Petrov of Rosmedtekhnologiy"
š·šŗSt Petersburg, Russian Federation