Clinical Trials List
Protocol NumberI4T-JE-JVCW
NCT Number(ClinicalTrials.gov Identfier)NCT02539225
2015-09-15 - 2019-02-28
Phase II
Terminated5
ICD-10C16.0
Malignant neoplasm of cardia
ICD-10C16
Malignant neoplasm of stomach
A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of S-1 and Oxaliplatin With or Without Ramucirumab as First-line Therapy Followed by Paclitaxel With Ramucirumab as Second-line Therapy in Patients With Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
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Trial Applicant
ELI LILLY AND COMPANY(TAIWAN), INC.
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Sponsor
Eli Lilly and Company
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yi-Ping Hung Division of Hematology & Oncology
- Chung-Pin Li Division of Hematology & Oncology
- Rheun-Chuan Lee Division of Hematology & Oncology
- Ming-Huang Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Yan-Shen Shan Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Nai-Jung Chiang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Che-Hung Lin Division of Hematology & Oncology
- Chang-Fang Chiu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Wen-Chi Shen Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
- Wen-Chi Chou Division of Hematology & Oncology
- Hung-Chih Hsu Division of Hematology & Oncology
- Tsai-Sheng Yang Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
20 Stop recruiting
Audit
None
Co-Principal Investigator
- Ann-Lii Cheng Division of Hematology & Oncology
- JHE-CYUAN GUO Division of Hematology & Oncology
- SUNG-HSIN KUO Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- Hsiang-Fong Kao Division of Hematology & Oncology
- 陳國興 Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- TA-CHEN HUANG Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- 呂理駿 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Objectives
The main purpose of this study is to evaluate the effectiveness of S-1 and oxaliplatin with or without ramucirumab as first line therapy in participants with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Test Drug
Ramucirumab
Active Ingredient
Ramucirumab
Dosage Form
IV
Dosage
500
Endpoints
Primary Outcome Measures :
1. Progression Free Survival (PFS) [ Time Frame: Randomization to Radiographic Documentation of Progression or Death Due to Any Cause (Up to 25 Months) ]
PFS is defined as the time from the date of randomization until the date of objectively determined progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause, whichever is first. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 millimeter (mm) or the appearance of ≥1 new lesions was progression. Participants who did not progress, were lost to follow-up were censored at the day of their last adequate tumor assessment.
Secondary Outcome Measures :
1. Progression-free Survival to the Second Disease Progression (PFS 2) [ Time Frame: Randomization to Second Radiographic Documentation of Progression or Death Due to Any Cause (Up to 31 Months) ]
Progression-free survival 2 (PFS2) is defined as the time from the date of randomization to second disease progression (defined as the date of first tumor assessment observing PD defined by RECIST v.1.1, after the start of second-line therapy using the last tumor assessment before starting the second-line therapy (RAM+PTX) as the baseline assessment), or death of any cause, whichever occurs first. If the second-line therapy was not started, the OS will be substituted for PFS2. If a post-discontinuation therapy was started before observing PD after the start of second-line therapy. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. PFS2 will be censored at the date of the last adequate tumor assessment on or before staring the post-discontinuation therapy.
2. Overall Survival (OS) [ Time Frame: Randomization to Death Due to Any Cause (Up to 31 Months) ]
Overall survival is defined as time from the date of randomization to the date of death from any cause. If the patient was alive at the cut-off for analysis (or lost to follow-up), OS data were censored for analysis on the last date the patient was known to be alive.
3. Percentage of Participants With Objective Response Rate (ORR) [ Time Frame: Randomization to Disease Progression (Up to 25 Months) ]
The ORR is the number of all participants with Partial Response (PR) or Complete Response (CR) according to RECIST v1.1 from the start of the treatment until disease progression/recurrence. CR is defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 mm. PR is defined as ≥30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 mm or the appearance of ≥1 new lesions was progression.
4. Disease Control Rate (DCR) [ Time Frame: Randomization to Disease Progression (Up to 25 Months) ]
Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 mm or the appearance of ≥1 new lesions was progression.
5. Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part A [ Time Frame: Cycle 1 Day 1 & 8 Predose, Cycle 2 Day 1 Predose, Cycle 3 Day 1 Predose, Cycle 5 Day 1 Predose, Cycle 9 Day 1 Predose ]
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part A.
6. Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part B [ Time Frame: Cycle 1 Day 1 predose, Cycle 2 Day 1 predose ]
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part B.
7. Number of Participants With Anti-Ramucirumab Antibodies [ Time Frame: Baseline through 25 months ]
Participant is considered as treatment emergent anti-drug antibody (TE ADA) positive if the participant has at least one post baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post baseline result of ADA Present with titer >= 20.
1. Progression Free Survival (PFS) [ Time Frame: Randomization to Radiographic Documentation of Progression or Death Due to Any Cause (Up to 25 Months) ]
PFS is defined as the time from the date of randomization until the date of objectively determined progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause, whichever is first. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 millimeter (mm) or the appearance of ≥1 new lesions was progression. Participants who did not progress, were lost to follow-up were censored at the day of their last adequate tumor assessment.
Secondary Outcome Measures :
1. Progression-free Survival to the Second Disease Progression (PFS 2) [ Time Frame: Randomization to Second Radiographic Documentation of Progression or Death Due to Any Cause (Up to 31 Months) ]
Progression-free survival 2 (PFS2) is defined as the time from the date of randomization to second disease progression (defined as the date of first tumor assessment observing PD defined by RECIST v.1.1, after the start of second-line therapy using the last tumor assessment before starting the second-line therapy (RAM+PTX) as the baseline assessment), or death of any cause, whichever occurs first. If the second-line therapy was not started, the OS will be substituted for PFS2. If a post-discontinuation therapy was started before observing PD after the start of second-line therapy. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. PFS2 will be censored at the date of the last adequate tumor assessment on or before staring the post-discontinuation therapy.
2. Overall Survival (OS) [ Time Frame: Randomization to Death Due to Any Cause (Up to 31 Months) ]
Overall survival is defined as time from the date of randomization to the date of death from any cause. If the patient was alive at the cut-off for analysis (or lost to follow-up), OS data were censored for analysis on the last date the patient was known to be alive.
3. Percentage of Participants With Objective Response Rate (ORR) [ Time Frame: Randomization to Disease Progression (Up to 25 Months) ]
The ORR is the number of all participants with Partial Response (PR) or Complete Response (CR) according to RECIST v1.1 from the start of the treatment until disease progression/recurrence. CR is defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 mm. PR is defined as ≥30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 mm or the appearance of ≥1 new lesions was progression.
4. Disease Control Rate (DCR) [ Time Frame: Randomization to Disease Progression (Up to 25 Months) ]
Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 mm or the appearance of ≥1 new lesions was progression.
5. Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part A [ Time Frame: Cycle 1 Day 1 & 8 Predose, Cycle 2 Day 1 Predose, Cycle 3 Day 1 Predose, Cycle 5 Day 1 Predose, Cycle 9 Day 1 Predose ]
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part A.
6. Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part B [ Time Frame: Cycle 1 Day 1 predose, Cycle 2 Day 1 predose ]
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part B.
7. Number of Participants With Anti-Ramucirumab Antibodies [ Time Frame: Baseline through 25 months ]
Participant is considered as treatment emergent anti-drug antibody (TE ADA) positive if the participant has at least one post baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post baseline result of ADA Present with titer >= 20.
Inclution Criteria
Inclusion Criteria:
• Have a histopathologically or cytologically confirmed diagnosis of metastatic gastric or GEJ adenocarcinoma. Participants with esophageal cancer are not eligible.
• Have not received any prior first-line systemic therapy for gastric or GEJ adenocarcinoma (prior adjuvant or neoadjuvant therapy is permitted). Participants whose disease has progressed after >24 weeks following the last dose of systemic treatment in the adjuvant/neoadjuvant setting are eligible.
• Have measurable or nonmeasurable but evaluable disease determined using guidelines in Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1).
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale at baseline.
• Have adequate organ function.
• Have an estimated life expectancy of ≥12 weeks in the judgment of the investigator.
• Eligible participants of reproductive potential (both sexes) must agree to use contraception (hormonal or barrier methods) during the study period and at least 6 months after the last dose of study treatment or longer if required per local regulations.
• Are willing to provide a blood sample for research purposes. Submission of a blood sample is mandatory for participation in this study unless restricted by local regulations or ethical review boards (ERBs); submission of a tumor tissue sample is optional.
• Have a histopathologically or cytologically confirmed diagnosis of metastatic gastric or GEJ adenocarcinoma. Participants with esophageal cancer are not eligible.
• Have not received any prior first-line systemic therapy for gastric or GEJ adenocarcinoma (prior adjuvant or neoadjuvant therapy is permitted). Participants whose disease has progressed after >24 weeks following the last dose of systemic treatment in the adjuvant/neoadjuvant setting are eligible.
• Have measurable or nonmeasurable but evaluable disease determined using guidelines in Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1).
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale at baseline.
• Have adequate organ function.
• Have an estimated life expectancy of ≥12 weeks in the judgment of the investigator.
• Eligible participants of reproductive potential (both sexes) must agree to use contraception (hormonal or barrier methods) during the study period and at least 6 months after the last dose of study treatment or longer if required per local regulations.
• Are willing to provide a blood sample for research purposes. Submission of a blood sample is mandatory for participation in this study unless restricted by local regulations or ethical review boards (ERBs); submission of a tumor tissue sample is optional.
Exclusion Criteria
Exclusion Criteria:
• Participants with human epidermal growth factor receptor 2 (HER2)-positive status as determined per local standards. Participants with a negative test or having an indeterminate result due to any reason are eligible, provided these participants are not eligible for treatment directed against tumors which overexpress HER2.
• Have radiation therapy within 14 days prior to randomization. Any lesion requiring palliative radiation or which has been previously irradiated cannot be considered for response assessment.
• Have documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.
• Have undergone major surgery within 28 days prior to randomization.
• Are currently enrolled in, or discontinued study drug within the last 28 days from, a clinical trial involving an investigational product or non-approved use of a drug or device (other than the study drug used in this study), or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Participants participating in surveys or observational studies are eligible to participate in this study.
• Are pregnant or breast feeding. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to first dose of study treatment.
• Have any prior malignancies.
• Have any condition (eg, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures or suggest that the participant is, in the investigator's opinion, not an appropriate candidate for the study.
• Participants with human epidermal growth factor receptor 2 (HER2)-positive status as determined per local standards. Participants with a negative test or having an indeterminate result due to any reason are eligible, provided these participants are not eligible for treatment directed against tumors which overexpress HER2.
• Have radiation therapy within 14 days prior to randomization. Any lesion requiring palliative radiation or which has been previously irradiated cannot be considered for response assessment.
• Have documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.
• Have undergone major surgery within 28 days prior to randomization.
• Are currently enrolled in, or discontinued study drug within the last 28 days from, a clinical trial involving an investigational product or non-approved use of a drug or device (other than the study drug used in this study), or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Participants participating in surveys or observational studies are eligible to participate in this study.
• Are pregnant or breast feeding. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to first dose of study treatment.
• Have any prior malignancies.
• Have any condition (eg, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures or suggest that the participant is, in the investigator's opinion, not an appropriate candidate for the study.
The Estimated Number of Participants
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Taiwan
30 participants
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Global
213 participants
