Back to resultsE7050 in Combination With Cisplatin and Capecitabine Versus Cisplatin and Capecitabine Alone in Patients With Advanced or Metastatic Solid Tumors and Previously Untreated Gastric Cancer
Primary Purpose
Advanced or Metastatic Solid Tumors, Previously Untreated Gastric Cancer
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
E7050
cisplatin
capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Advanced or Metastatic Solid Tumors focused on measuring Cancer, Solid Tumors, Gastric, Phase I, Phase II
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed, unresectable, locally advanced or metastatic gastric cancer, including adenocarcinoma of the gastroesophageal junction (Phase II). For the Phase Ib portion, any unresectable, locally advanced or metastatic solid tumor;
- ECOG PS of 0-1;
- Blood pressure must be well-controlled. Patients must have no history of hypertensive crisis or hypertensive encephalopathy; Adequate end organ function
Exclusion Criteria
- Gastric cancer patients who have had a complete gastrectomy;
- Patients with known HER2 over-expressing advanced or metastatic gastric cancer;
- Previously received E7050, its chemical derivatives, anti-cMet, anti-angiogenic therapy, (prior anti-angiogenic therapy is permitted in Phase Ib only).
- For Phase Ib prior systemic therapy is allowed as long as PS and end organ function meet entry criteria;
- For Phase II no prior palliative chemotherapy is permitted. Adjuvant/neoadjuvant chemotherapy is permitted if less than 12 months have elapsed between the end of adjuvant/neoadjuvant therapy and first recurrence;
- Known central nervous system lesions, except for asymptomatic non-progressing, treated brain metastases. Treatment for brain mets, but have been completed at least 4 weeks prior to Day 1
- Palliative radiotherapy is not permitted throughout the study period. Prior palliative radiotherapy within 30 days prior to commencing study treatment;
- Clinically significant hemoptysis;
- Patients with known dihydropyrimidine dehydrogenase deficiency;
- Patients with clinically significant hearing loss that may be further diminished by treatment with cisplatin plus capecitabine (significance of hearing loss to be determined by the Investigator;
- Serious non-healing wound, ulcer, or active bone fracture;
- Major surgical procedure, open biopsy, or significant traumatic injury within the 21 days prior to commencing study treatment;
- Clinically significant gastrointestinal bleeding within 6 months prior to first dose.
Sites / Locations
- Arizona Oncology Associates, PC - CASA
- Boca Raton Clinical Research Associates, Inc
- Robert H. Lurie Comprenhensive Cancer Center of Northwestern University
- University of Michigan Comprehensive Cancer Center
- Barbara Ann Karmanos Cancer Institute
- Henry Ford Medical Center
- University of North Carolina at Chapel Hill
- Duke University Medical Center
- Mercy Cancer Centerr at St. Anne
- Chelyabinsk Regional Oncology Dispensary
- GOU VPO St-Petersburg SMA n/a Mechnikov Fed. Agen. of Healthcare and Social Developm.
- FSI "SRC of Oncology n. a. N.N.Petrov of Rosmedtekhnologiy"
- SI Dnipropetrovsk Medical Academy of MOHU ch of Oncology and Medical Radiology
- Municipal Clinical Medical and Prophylactic Institution Donetsk Regional Antitumor Centre
- Kyiv City Clinical Oncological Center
- Lviv State Oncol. Reg. Treatment and Diagnostic Center
- Barts and the London NHS Trust
- Sarah Cannon Research UK
- The Christie NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Phase Ib: Cohort 1 and 2 and 3
Phase II: Arm 1; E7050 + cisplatin+ capecitabine
Arm Description
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; MTD E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine
Outcomes
Primary Outcome Measures
Area Under The Concentration-Time Curve (AUC) From 0 to 24 Hours of Golvatinib
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 nanograms·hour/milliter (ng·h/mL).
Maximum Concentration (Cmax) of Golvatinib
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)
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.
Time to Maximum Concentration (Tmax) of Golvatinib
Tmax was defined as the time at which Cmax was observed for golvatinib in combination with cisplatin and capecitabine.
Secondary Outcome Measures
Overall Response Rate (ORR)
The study was terminated prior to enrollment in Phase 2 so this outcome measure was not conducted.
Time to Progression (TTP)
The study was terminated prior to enrollment in Phase 2 so this outcome measure was not conducted.
Full Information
NCT ID
NCT01355302
First Posted
May 16, 2011
Last Updated
April 7, 2017
Sponsor
Eisai Inc.
Collaborators
Quintiles, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01355302
Brief Title
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
Official Title
An Open-Label, Multicenter, Randomized, Phase Ib/II Study of 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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
Sites not recruiting
Study Start Date
November 2011 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
July 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.
Collaborators
Quintiles, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced or Metastatic Solid Tumors, Previously Untreated Gastric Cancer
Keywords
Cancer, Solid Tumors, Gastric, Phase I, Phase II
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase Ib: Cohort 1 and 2 and 3
Arm Type
Experimental
Arm Description
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
Arm Title
Phase II: Arm 1; E7050 + cisplatin+ capecitabine
Arm Type
Active Comparator
Arm Description
Phase II: Arm 1; MTD E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine
Intervention Type
Drug
Intervention Name(s)
E7050
Intervention Description
E7050 given orally at either 200, 300, or 400 mg once daily.
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Description
Cisplatin will be administered at 80 mg/m2 by intravenous infusion over 60 minutes on Day 1 of each 21-day treatment cycle.
Intervention Type
Drug
Intervention Name(s)
capecitabine
Intervention Description
Capecitabine will be administered at 1000 mg/m2 orally, twice daily (2000 mg/m2 total daily dose) on Days 1 through 14 of each 21-day treatment cycle.
Primary Outcome Measure Information:
Title
Area Under The Concentration-Time Curve (AUC) From 0 to 24 Hours of Golvatinib
Description
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 nanograms·hour/milliter (ng·h/mL).
Time Frame
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.
Title
Maximum Concentration (Cmax) of Golvatinib
Description
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).
Time Frame
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.
Title
Number of Participants With a Treatment-Emergent Adverse Event (TEAE)
Description
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.
Time Frame
From date of first dose up to 30 days after the last dose of study treatment, up to approximately 1 year 1 month.
Title
Time to Maximum Concentration (Tmax) of Golvatinib
Description
Tmax was defined as the time at which Cmax was observed for golvatinib in combination with cisplatin and capecitabine.
Time Frame
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.
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
The study was terminated prior to enrollment in Phase 2 so this outcome measure was not conducted.
Time Frame
Until disease progression or death for 3 years
Title
Time to Progression (TTP)
Description
The study was terminated prior to enrollment in Phase 2 so this outcome measure was not conducted.
Time Frame
Until disease progression or death for 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Histologically confirmed, unresectable, locally advanced or metastatic gastric cancer, including adenocarcinoma of the gastroesophageal junction (Phase II). For the Phase Ib portion, any unresectable, locally advanced or metastatic solid tumor;
ECOG PS of 0-1;
Blood pressure must be well-controlled. Patients must have no history of hypertensive crisis or hypertensive encephalopathy; Adequate end organ function
Exclusion Criteria
Gastric cancer patients who have had a complete gastrectomy;
Patients with known HER2 over-expressing advanced or metastatic gastric cancer;
Previously received E7050, its chemical derivatives, anti-cMet, anti-angiogenic therapy, (prior anti-angiogenic therapy is permitted in Phase Ib only).
For Phase Ib prior systemic therapy is allowed as long as PS and end organ function meet entry criteria;
For Phase II no prior palliative chemotherapy is permitted. Adjuvant/neoadjuvant chemotherapy is permitted if less than 12 months have elapsed between the end of adjuvant/neoadjuvant therapy and first recurrence;
Known central nervous system lesions, except for asymptomatic non-progressing, treated brain metastases. Treatment for brain mets, but have been completed at least 4 weeks prior to Day 1
Palliative radiotherapy is not permitted throughout the study period. Prior palliative radiotherapy within 30 days prior to commencing study treatment;
Clinically significant hemoptysis;
Patients with known dihydropyrimidine dehydrogenase deficiency;
Patients with clinically significant hearing loss that may be further diminished by treatment with cisplatin plus capecitabine (significance of hearing loss to be determined by the Investigator;
Serious non-healing wound, ulcer, or active bone fracture;
Major surgical procedure, open biopsy, or significant traumatic injury within the 21 days prior to commencing study treatment;
Clinically significant gastrointestinal bleeding within 6 months prior to first dose.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melissa Versola
Organizational Affiliation
Quintiles, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Oncology Associates, PC - CASA
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85715
Country
United States
Facility Name
Boca Raton Clinical Research Associates, Inc
City
Plantation
State/Province
Florida
ZIP/Postal Code
33324
Country
United States
Facility Name
Robert H. Lurie Comprenhensive Cancer Center of Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48084
Country
United States
Facility Name
Henry Ford Medical Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapell Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Mercy Cancer Centerr at St. Anne
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43623
Country
United States
Facility Name
Chelyabinsk Regional Oncology Dispensary
City
Chelyabinsk
ZIP/Postal Code
454087
Country
Russian Federation
Facility Name
GOU VPO St-Petersburg SMA n/a Mechnikov Fed. Agen. of Healthcare and Social Developm.
City
St Petersburg
ZIP/Postal Code
195067
Country
Russian Federation
Facility Name
FSI "SRC of Oncology n. a. N.N.Petrov of Rosmedtekhnologiy"
City
St Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
SI Dnipropetrovsk Medical Academy of MOHU ch of Oncology and Medical Radiology
City
Dnipropetrovsk
ZIP/Postal Code
49102
Country
Ukraine
Facility Name
Municipal Clinical Medical and Prophylactic Institution Donetsk Regional Antitumor Centre
City
Donetsk
ZIP/Postal Code
83092
Country
Ukraine
Facility Name
Kyiv City Clinical Oncological Center
City
Kyiv
ZIP/Postal Code
3115
Country
Ukraine
Facility Name
Lviv State Oncol. Reg. Treatment and Diagnostic Center
City
Lviv
ZIP/Postal Code
79031
Country
Ukraine
Facility Name
Barts and the London NHS Trust
City
London
State/Province
Greater London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Facility Name
Sarah Cannon Research UK
City
London
State/Province
Greater London
ZIP/Postal Code
W1G 6AD
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Manchester
State/Province
Greater Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
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
We'll reach out to this number within 24 hrs