A Study of Ramucirumab Combination Therapy in Japanese Participants Who Have Advanced Stomach Cancer
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02359058
Collaborator
(none)
18
4
3
21
4.5
0.2
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
18 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date
:
Feb 1, 2015
Actual Primary Completion Date
:
Jul 1, 2016
Actual Study Completion Date
:
Nov 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Ramucirumab + Capecitabine + Cisplatin 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. |
Drug: Ramucirumab
Administered IV
Other Names:
Drug: Capecitabine
Administered orally
Drug: Cisplatin
Administered IV
|
| Other: Ramucirumab + S-1 + Cisplatin 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. |
Drug: Ramucirumab
Administered IV
Other Names:
Drug: Cisplatin
Administered IV
Drug: S-1
Administered orally
|
| Other: Ramucirumab + S-1 + Oxaliplatin 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. |
Drug: Ramucirumab
Administered IV
Other Names:
Drug: S-1
Administered orally
Drug: Oxaliplatin
Administered IV
|
Outcome Measures
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 [First Dose to Study Completion Plus 30-Day Safety Follow-Up (Up To 22 Months)]
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 [Day 1, Day 8, Day 43, Day 50, Day 85 and Day 92: End of Infusion]
Maximum Serum Concentration (Cmax) of Ramucirumab.
- Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) of Ramucirumab [Day 8, Day 22, Day 29, Day 43, Day 50, Day 64, Day 71, Day 85, Day 92 and Day 106: Pre-Dose]
Minimum Serum Concentration (Cmin) of Ramucirumab.
- Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate) [First Dose to Date of Objective Progressive Disease or Death Due to Any Cause (Up To 22 Months)]
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) [First dose to study completion plus 30-day safety follow-up (Up To 22 Months)]
Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group.
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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. | Aichi | Japan | 464-8681 | |
| 2 | 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. | Chiba | Japan | 277-8577 | |
| 3 | 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. | Ehime | Japan | 791-0280 | |
| 4 | 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 | Osaka | Japan | 565-0871 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: 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), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02359058
Other Study ID Numbers:
- 15532
- I4T-JE-JVCX
First Posted:
Feb 9, 2015
Last Update Posted:
Jan 24, 2018
Last Verified:
Jul 1, 2017
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Participants were considered completed if they either completed Cycle 1 of study drug or discontinued study drug due to a dose limiting toxicity (DLT) during Cycle 1. |
| Arm/Group Title | Ramucirumab + Capecitabine + Cisplatin | Ramucirumab + S-1 + Cisplatin | Ramucirumab + S-1 + Oxaliplatin |
|---|---|---|---|
| Arm/Group Description | Ramucirumab 8 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. |
| Period Title: Overall Study | |||
| STARTED | 6 | 6 | 6 |
| Received at Least 1 Dose of Study Drug | 6 | 6 | 6 |
| COMPLETED | 6 | 6 | 6 |
| NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Ramucirumab + Capecitabine + Cisplatin | Ramucirumab + S-1 + Cisplatin | Ramucirumab + S-1 + Oxaliplatin | Total |
|---|---|---|---|---|
| Arm/Group Description | Ramucirumab 8 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. | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 18 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
57.5
(10.93)
|
60.3
(7.06)
|
62.7
(6.98)
|
60.2
(8.30)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
4
66.7%
|
6
100%
|
0
0%
|
10
55.6%
|
| Male |
2
33.3%
|
0
0%
|
6
100%
|
8
44.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
6
100%
|
6
100%
|
6
100%
|
18
100%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
6
100%
|
6
100%
|
6
100%
|
18
100%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | ||||
| Japan |
6
100%
|
6
100%
|
6
100%
|
18
100%
|
Outcome Measures
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants who received at least one dose of study drug. |
| Arm/Group Title | Ramucirumab + Capecitabine + Cisplatin | Ramucirumab + S-1 + Cisplatin | Ramucirumab + S-1 + Oxaliplatin |
|---|---|---|---|
| Arm/Group Description | Ramucirumab 8 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. |
| Measure Participants | 6 | 6 | 6 |
| Count of Participants [Participants] |
1
16.7%
|
2
33.3%
|
2
33.3%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants who received at least one dose of the study drug and had evaluable ramucirumab PK data. |
| Arm/Group Title | Ramucirumab + Capecitabine + Cisplatin | Ramucirumab + S-1 + Cisplatin | Ramucirumab + S-1 + Oxaliplatin |
|---|---|---|---|
| Arm/Group Description | Ramucirumab 8 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. |
| Measure Participants | 6 | 6 | 6 |
| Day 1 |
149
(21)
|
139
(23)
|
137
(20)
|
| Day 8 |
229
(24)
|
200
(21)
|
211
(11)
|
| Day 43 |
205
(24)
|
253
(11)
|
180
(28)
|
| Day 50 |
273
(24)
|
249
(24)
|
207
(12)
|
| Day 85 |
NA
(NA)
|
272
(29)
|
NA
(NA)
|
| Day 92 |
NA
(NA)
|
289
(22)
|
NA
(NA)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants who received at least one dose of the study drug and had evaluable ramucirumab PK data. |
| Arm/Group Title | Ramucirumab + Capecitabine + Cisplatin | Ramucirumab + S-1 + Cisplatin | Ramucirumab + S-1 + Oxaliplatin |
|---|---|---|---|
| Arm/Group Description | Ramucirumab 8 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. |
| Measure Participants | 6 | 6 | 6 |
| Day 8 |
43.8
(16)
|
51.6
(28)
|
43.2
(30)
|
| Day 22 |
40.9
(21)
|
63.9
(33)
|
41.8
(37)
|
| Day 29 |
84.6
(24)
|
105
(19)
|
81.6
(28)
|
| Day 43 |
60.8
(27)
|
87.6
(34)
|
68.5
(41)
|
| Day 50 |
91.7
(32)
|
91.3
(28)
|
86.2
(17)
|
| Day 64 |
47.7
(31)
|
85.4
(34)
|
81.5
(11)
|
| Day 71 |
71.1
(34)
|
109
(13)
|
124
(5)
|
| Day 85 |
55.5
(34)
|
102
(18)
|
NA
(NA)
|
| Day 92 |
97.6
(24)
|
119
(14)
|
NA
(NA)
|
| Day 106 |
68.6
(52)
|
118
(12)
|
NA
(NA)
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants who received at least one dose of study drug and with measurable disease. |
| Arm/Group Title | Ramucirumab + Capecitabine + Cisplatin | Ramucirumab + S-1 + Cisplatin | Ramucirumab + S-1 + Oxaliplatin | Total |
|---|---|---|---|---|
| Arm/Group Description | Ramucirumab 8 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. | Ramucirumab + Capecitabine + Cisplatin, Ramucirumab + S-1 + Cisplatin and Ramucirumab + S-1 + Oxaliplatin. |
| Measure Participants | 5 | 1 | 5 | 11 |
| Number [Percentage of participants] |
20
333.3%
|
100
1666.7%
|
60
1000%
|
45.5
252.8%
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants who received at least one dose of the study drug and had evaluable immunogenicity data. |
| Arm/Group Title | Ramucirumab + Capecitabine + Cisplatin | Ramucirumab + S-1 + Cisplatin | Ramucirumab + S-1 + Oxaliplatin |
|---|---|---|---|
| Arm/Group Description | Ramucirumab 8 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. |
| Measure Participants | 6 | 6 | 6 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | First dose to study completion plus 30-day safety follow-up (Up To 22 Months) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Ramucirumab + Capecitabine + Cisplatin | Ramucirumab + S-1 + Cisplatin | Ramucirumab + S-1 + Oxaliplatin | |||
| Arm/Group Description | Ramucirumab 8 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. | |||
All Cause Mortality |
||||||
| Ramucirumab + Capecitabine + Cisplatin | Ramucirumab + S-1 + Cisplatin | Ramucirumab + S-1 + Oxaliplatin | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Ramucirumab + Capecitabine + Cisplatin | Ramucirumab + S-1 + Cisplatin | Ramucirumab + S-1 + Oxaliplatin | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/6 (16.7%) | 2/6 (33.3%) | 2/6 (33.3%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Enterocolitis | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Ileus | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Bile duct stenosis | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Infections and infestations | ||||||
| Sepsis | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Vascular disorders | ||||||
| Pelvic venous thrombosis | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Ramucirumab + Capecitabine + Cisplatin | Ramucirumab + S-1 + Cisplatin | Ramucirumab + S-1 + Oxaliplatin | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 6/6 (100%) | 5/6 (83.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 2/6 (33.3%) | 3 | 3/6 (50%) | 3 | 1/6 (16.7%) | 1 |
| Leukopenia | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Neutropenia | 4/6 (66.7%) | 8 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 20 |
| Thrombocytopenia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 3 |
| Ear and labyrinth disorders | ||||||
| Tinnitus | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Eye disorders | ||||||
| Lacrimation increased | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 4 |
| Ascites | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Constipation | 6/6 (100%) | 6 | 5/6 (83.3%) | 12 | 3/6 (50%) | 3 |
| Dental caries | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Diarrhoea | 0/6 (0%) | 0 | 3/6 (50%) | 5 | 2/6 (33.3%) | 2 |
| Gastrooesophageal reflux disease | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Haemorrhoids | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Nausea | 3/6 (50%) | 4 | 5/6 (83.3%) | 11 | 3/6 (50%) | 4 |
| Pancreatitis | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Stomatitis | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 2 | 1/6 (16.7%) | 1 |
| Upper gastrointestinal haemorrhage | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Vomiting | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 4 | 2/6 (33.3%) | 2 |
| General disorders | ||||||
| Fatigue | 1/6 (16.7%) | 1 | 3/6 (50%) | 4 | 0/6 (0%) | 0 |
| Malaise | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 5 |
| Oedema | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Oedema peripheral | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Pyrexia | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 3 | 2/6 (33.3%) | 2 |
| Hepatobiliary disorders | ||||||
| Hepatic function abnormal | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Liver disorder | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Portal vein thrombosis | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Infections and infestations | ||||||
| Angular cheilitis | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Cystitis | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Gingivitis | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Lung infection | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Paronychia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Rhinitis | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Tinea pedis | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Upper respiratory tract infection | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Arthropod bite | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Fall | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Heat illness | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Infusion related reaction | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 |
| Aspartate aminotransferase increased | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 |
| C-reactive protein increased | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Creatinine renal clearance decreased | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 |
| Gamma-glutamyltransferase increased | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 |
| Neutrophil count decreased | 1/6 (16.7%) | 2 | 5/6 (83.3%) | 15 | 2/6 (33.3%) | 5 |
| Platelet count decreased | 0/6 (0%) | 0 | 3/6 (50%) | 4 | 1/6 (16.7%) | 1 |
| Weight decreased | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 |
| White blood cell count decreased | 1/6 (16.7%) | 2 | 2/6 (33.3%) | 9 | 0/6 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 3/6 (50%) | 5 | 6/6 (100%) | 17 | 3/6 (50%) | 5 |
| Hypoalbuminaemia | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 3/6 (50%) | 3 |
| Hypokalaemia | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 3 | 0/6 (0%) | 0 |
| Hypomagnesaemia | 0/6 (0%) | 0 | 1/6 (16.7%) | 3 | 0/6 (0%) | 0 |
| Hyponatraemia | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 |
| Hypophosphataemia | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 | 1/6 (16.7%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Cancer pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Tumour pain | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Nervous system disorders | ||||||
| Dysgeusia | 0/6 (0%) | 0 | 4/6 (66.7%) | 4 | 1/6 (16.7%) | 1 |
| Headache | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Peripheral sensory neuropathy | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 3/6 (50%) | 5 |
| Psychiatric disorders | ||||||
| Insomnia | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 |
| Renal and urinary disorders | ||||||
| Proteinuria | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 1/6 (16.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Dysphonia | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Epistaxis | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Hiccups | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Oropharyngeal pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Rhinitis allergic | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Dry skin | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Miliaria | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Palmar-plantar erythrodysaesthesia syndrome | 3/6 (50%) | 3 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 |
| Pigmentation disorder | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Rash maculo-papular | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Skin hyperpigmentation | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Vascular disorders | ||||||
| Hypertension | 3/6 (50%) | 3 | 4/6 (66.7%) | 5 | 2/6 (33.3%) | 3 |
| Pelvic venous thrombosis | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Vascular pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Vasculitis | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02359058
Other Study ID Numbers:
- 15532
- I4T-JE-JVCX
First Posted:
Feb 9, 2015
Last Update Posted:
Jan 24, 2018
Last Verified:
Jul 1, 2017