Back to resultsA Study of Ramucirumab Combination Therapy in Japanese Participants Who Have Advanced Stomach Cancer
Primary Purpose
Stomach Neoplasms
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Ramucirumab
Capecitabine
Cisplatin
S-1
Oxaliplatin
Sponsored by
About this trial
This is an interventional treatment trial for Stomach Neoplasms
Eligibility Criteria
Inclusion Criteria:
- A histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma which is metastatic or locally advanced and unresectable. A participant with esophageal cancer is not eligible.
- Not have received prior first-line systemic chemotherapy for locally advanced and unresectable and/or metastatic disease. Participants whose disease has progressed after >6 months following the last dose of systemic treatment in the adjuvant/neoadjuvant setting are eligible.
- Measurable or nonmeasurable, but evaluable, disease, determined using guidelines in Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at the time of enrollment.
- The participant has adequate organ function.
- Resolution to Grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version [v]4.03) of all clinically significant toxic effects of prior locoregional therapy, surgery, or other anticancer.
- Female participants of childbearing potential must have a negative serum or urinary pregnancy. Have an estimated life expectancy of ≥12 weeks in the judgment of the investigator.
Exclusion Criteria:
- A significant bleeding disorder, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 12 weeks prior to enrollment.
- Uncontrolled arterial hypertension, despite standard medical management.
- A serious or nonhealing wound or peptic ulcer or bone fracture at enrollment.
- Undergone major surgery within 28 days prior to enrollment, or subcutaneous venous access device (reservoir) placement within 7 days prior to enrollment.
- Radiation therapy within 14 days prior to enrollment.
- Received any previous systemic therapy (including investigational agents) targeting vascular endothelial growth factor (VEGF) or the VEGF receptor signaling pathways.
- Cirrhosis at a level of Child-Pugh B (or worse); or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis.
- A serious illness or medical condition(s).
- Pregnant or breastfeeding.
- Dysphagia for oral medication.
- Known allergy or hypersensitivity to any study treatment.
- Human epidermal growth factor receptor (HER) 2 status of positive.
- Received treatment within 28 days of the initial dose of study drug with an investigational product or non-approved use of a drug or device.
Sites / Locations
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Other
Other
Other
Arm Label
Ramucirumab + Capecitabine + Cisplatin
Ramucirumab + S-1 + Cisplatin
Ramucirumab + S-1 + Oxaliplatin
Arm Description
Ramucirumab (8 milligram per kilogram (mg/kg) given intravenously (IV) on days 1 and 8 in combination with 1000 mg/square meter (m^2) capecitabine given orally twice a day on days 1 through 14 and 80 mg/m^2 cisplatin given IV on day 1 of each 21 day cycle (up to 6 cycles). Participants may continue to receive treatment until discontinuation criteria are met.
Ramucirumab 8 mg/kg given IV on days 1 and 8 of 21 day in combination with 40 mg/m^2 tegafur/gimeracil/oteracil (S-1) given orally twice a day on days 1 through 21 and 60 mg/m^2 cisplatin given IV on day 8 of each 35 day cycle (up to 8 cycles). Participants may continue to receive treatment until discontinuation criteria are met.
Ramucirumab 8 mg/kg given IV on days 1 and 8 in combination with 40 mg/m^2 S-1 given orally twice a day on days 1 through 14 and 100 mg/m^2 oxaliplatin given IV on day 1 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Outcomes
Primary Outcome Measures
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Clinically significant events were defined as serious adverse events (SAE). A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Secondary Outcome Measures
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Ramucirumab
Maximum Serum Concentration (Cmax) of Ramucirumab.
Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) of Ramucirumab
Minimum Serum Concentration (Cmin) of Ramucirumab.
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate)
Objective response rate (ORR) was defined as the percentage of randomized participants achieving a best confirmed overall response of CR or PR using Response Evaluation Criteria in Solid Tumors (RECIST v1). CR was defined as the disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as reference the baseline sum LD and no progression in non-target lesions.
Number of Participants With Treatment Emergent Anti-Ramucirumab Antibodies (TE-ADA)
Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group.
Full Information
NCT ID
NCT02359058
First Posted
February 4, 2015
Last Updated
January 2, 2018
Sponsor
Eli Lilly and Company
1. Study Identification
Unique Protocol Identification Number
NCT02359058
Brief Title
A Study of Ramucirumab Combination Therapy in Japanese Participants Who Have Advanced Stomach Cancer
Official Title
Phase 1b Study of Ramucirumab in Combination With Fluoropyrimidines and Platinum-Based Agents in Japanese Patients With Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
February 2015 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
November 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and antitumor response of ramucirumab in combination with platinum/fluoropyrimidine regimens in Japanese participants with advanced gastric/gastrooesophageal junction cancer who have not received chemotherapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stomach Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ramucirumab + Capecitabine + Cisplatin
Arm Type
Other
Arm Description
Ramucirumab (8 milligram per kilogram (mg/kg) given intravenously (IV) on days 1 and 8 in combination with 1000 mg/square meter (m^2) capecitabine given orally twice a day on days 1 through 14 and 80 mg/m^2 cisplatin given IV on day 1 of each 21 day cycle (up to 6 cycles). Participants may continue to receive treatment until discontinuation criteria are met.
Arm Title
Ramucirumab + S-1 + Cisplatin
Arm Type
Other
Arm Description
Ramucirumab 8 mg/kg given IV on days 1 and 8 of 21 day in combination with 40 mg/m^2 tegafur/gimeracil/oteracil (S-1) given orally twice a day on days 1 through 21 and 60 mg/m^2 cisplatin given IV on day 8 of each 35 day cycle (up to 8 cycles). Participants may continue to receive treatment until discontinuation criteria are met.
Arm Title
Ramucirumab + S-1 + Oxaliplatin
Arm Type
Other
Arm Description
Ramucirumab 8 mg/kg given IV on days 1 and 8 in combination with 40 mg/m^2 S-1 given orally twice a day on days 1 through 14 and 100 mg/m^2 oxaliplatin given IV on day 1 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Intervention Type
Drug
Intervention Name(s)
Ramucirumab
Other Intervention Name(s)
LY3009806, IMC-1121B
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Administered orally
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
S-1
Intervention Description
Administered orally
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Administered IV
Primary Outcome Measure Information:
Title
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Description
Clinically significant events were defined as serious adverse events (SAE). A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time Frame
First Dose to Study Completion Plus 30-Day Safety Follow-Up (Up To 22 Months)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Ramucirumab
Description
Maximum Serum Concentration (Cmax) of Ramucirumab.
Time Frame
Day 1, Day 8, Day 43, Day 50, Day 85 and Day 92: End of Infusion
Title
Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) of Ramucirumab
Description
Minimum Serum Concentration (Cmin) of Ramucirumab.
Time Frame
Day 8, Day 22, Day 29, Day 43, Day 50, Day 64, Day 71, Day 85, Day 92 and Day 106: Pre-Dose
Title
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate)
Description
Objective response rate (ORR) was defined as the percentage of randomized participants achieving a best confirmed overall response of CR or PR using Response Evaluation Criteria in Solid Tumors (RECIST v1). CR was defined as the disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as reference the baseline sum LD and no progression in non-target lesions.
Time Frame
First Dose to Date of Objective Progressive Disease or Death Due to Any Cause (Up To 22 Months)
Title
Number of Participants With Treatment Emergent Anti-Ramucirumab Antibodies (TE-ADA)
Description
Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group.
Time Frame
First dose to study completion plus 30-day safety follow-up (Up To 22 Months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
A histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma which is metastatic or locally advanced and unresectable. A participant with esophageal cancer is not eligible.
Not have received prior first-line systemic chemotherapy for locally advanced and unresectable and/or metastatic disease. Participants whose disease has progressed after >6 months following the last dose of systemic treatment in the adjuvant/neoadjuvant setting are eligible.
Measurable or nonmeasurable, but evaluable, disease, determined using guidelines in Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at the time of enrollment.
The participant has adequate organ function.
Resolution to Grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version [v]4.03) of all clinically significant toxic effects of prior locoregional therapy, surgery, or other anticancer.
Female participants of childbearing potential must have a negative serum or urinary pregnancy. Have an estimated life expectancy of ≥12 weeks in the judgment of the investigator.
Exclusion Criteria:
A significant bleeding disorder, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 12 weeks prior to enrollment.
Uncontrolled arterial hypertension, despite standard medical management.
A serious or nonhealing wound or peptic ulcer or bone fracture at enrollment.
Undergone major surgery within 28 days prior to enrollment, or subcutaneous venous access device (reservoir) placement within 7 days prior to enrollment.
Radiation therapy within 14 days prior to enrollment.
Received any previous systemic therapy (including investigational agents) targeting vascular endothelial growth factor (VEGF) or the VEGF receptor signaling pathways.
Cirrhosis at a level of Child-Pugh B (or worse); or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis.
A serious illness or medical condition(s).
Pregnant or breastfeeding.
Dysphagia for oral medication.
Known allergy or hypersensitivity to any study treatment.
Human epidermal growth factor receptor (HER) 2 status of positive.
Received treatment within 28 days of the initial dose of study drug with an investigational product or non-approved use of a drug or device.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician.
City
Aichi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician.
City
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician.
City
Ehime
ZIP/Postal Code
791-0280
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician
City
Osaka
ZIP/Postal Code
565-0871
Country
Japan
12. IPD Sharing Statement
Learn more about this trial
A Study of Ramucirumab Combination Therapy in Japanese Participants Who Have Advanced Stomach Cancer
We'll reach out to this number within 24 hrs