A Phase 2 interventional study of Ramucirumab and Placebo in Metastatic Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, sponsored by Eli Lilly and Company. Completed at 34 sites in 3 countries. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2022-03-08.
Sponsored by Eli Lilly and Company · Phase 2, Interventional, and Treatment
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.
2,004 studies on the registry are indexed under Adenocarcinoma; 375 are open to participants now.
This study's enrollment of 191 is above the median of 45 across 1,553 interventional studies indexed under Adenocarcinoma.
Browse Adenocarcinoma studies →Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.
Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
(Part A) Ramucirumab intravenously (IV) on day 1 and day 8 along with S-1 by mouth (PO) on days 1-14 and oxaliplatin IV on day 1 of each 21 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met then move to Part B. (Part B) Ramucirumab IV on day 1 and day 15 along with paclitaxel IV on day 1, 8, and 15 of each 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
Drug: Ramucirumab · Drug: S-1 · Drug: Oxaliplatin · Drug: Paclitaxel
(Part A) Placebo IV on day 1 and day 8 along with S-1 PO on days 1-14 and oxaliplatin IV on day 1 of each 21 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met then move to Part B. (Part B) Ramucirumab IV on day 1 and day 15 along with paclitaxel IV on day 1, 8, and 15 of each 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
Drug: Ramucirumab · Drug: Placebo · Drug: S-1 · Drug: Oxaliplatin · Drug: Paclitaxel
Administered IV
Also known as: LY3009806, IMC-1121B, Cyramza
Administered IV
Administered PO
Administered IV
Administered IV
Progression Free Survival (PFS)
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.
Time frame: Randomization to Radiographic Documentation of Progression or Death Due to Any Cause (Up to 25 Months)
Progression-free Survival to the Second Disease Progression (PFS 2)
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.
Time frame: Randomization to Second Radiographic Documentation of Progression or Death Due to Any Cause (Up to 31 Months)
Overall Survival (OS)
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.
Time frame: Randomization to Death Due to Any Cause (Up to 31 Months)
Percentage of Participants With Objective Response Rate (ORR)
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.
Time frame: Randomization to Disease Progression (Up to 25 Months)
Disease Control Rate (DCR)
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.
Time frame: Randomization to Disease Progression (Up to 25 Months)
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part A
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 B
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part B.
Time frame: Cycle 1 Day 1 predose, Cycle 2 Day 1 predose
Number of Participants With Anti-Ramucirumab Antibodies
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.
Time frame: Baseline through 25 months
Completers are defined as participants who died or those who were alive and off treatment at study completion.
| Milestone | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin |
|---|---|---|
| Started | 97 | 94 |
| Received any quantity of study drug | 96 | 93 |
| Completed | 77 | 78 |
| Not completed | 20 | 16 |
| Withdrew: Adverse event | 13 | 4 |
| Withdrew: Withdrawal by subject | 2 | 4 |
| Withdrew: Physician decision | 4 | 7 |
| Withdrew: Did not receive study drug | 1 | 1 |
| Milestone | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin |
|---|---|---|
| Started | 63 | 66 |
| Completed | 58 | 64 |
| Not completed | 5 | 2 |
| Withdrew: Progressive disease | 1 | 1 |
| Withdrew: Adverse event | 1 | 1 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Withdrew: Physician decision | 2 | 0 |
| Milestone | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin |
|---|---|---|
| Started | 58 | 64 |
| Completed | 54 | 48 |
| Not completed | 4 | 16 |
| Withdrew: Adverse event | 4 | 4 |
| Withdrew: Withdrawal by subject | 0 | 3 |
| Withdrew: Physician decision | 0 | 9 |
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.
| Months | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin |
|---|---|---|
| Progression Free Survival (PFS) | 6.34 (5.65 to 6.93) | 6.74 (5.75 to 7.13) |
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.
| Months | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin |
|---|---|---|
| Progression-free Survival to the Second Disease Progression (PFS 2) | 10.94 (9.63 to 12.52) | 11.99 (9.82 to 13.83) |
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.
| Months | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin |
|---|---|---|
| Overall Survival (OS) | 14.65 (12.39 to 15.67) | 14.26 (13.83 to 17.31) |
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.
| percentage of participants | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin |
|---|---|---|
| Percentage of Participants With Objective Response Rate (ORR) | 58.2 (49.7 to 66.7) | 50.0 (41.3 to 58.7) |
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.
| percentage of participants | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin |
|---|---|---|
| Disease Control Rate (DCR) | 90.9 (85.9 to 95.9) | 87 (81.2 to 92.9) |
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part A.
| Microgram per milliliter (ug/mL) | Ramucirumab + S-1 + Oxaliplatin - Part A |
|---|---|
| Cycle 1 Day 1 | NA ± NA |
| Cycle 1 Day 8 | 42.6 ± 32 |
| Cycle 2 Day 1 | 41.4 ± 40 |
| Cycle 3 Day 1 | 59.4 ± 51 |
| Cycle 5 Day 1 | 83.6 ± 37 |
| Cycle 9 Day 1 | 94.6 ± 38 |
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part B.
| Microgram per milliliter (ug/mL) | Ramucirumab + S-1 + Oxaliplatin Part B | Placebo + S-1 + Oxaliplatin - Part B |
|---|---|---|
| Cycle 1 Day 1 | 52.0 ± 65 | NA ± NA |
| Cycle 2 Day 1 | 58.1 ± 40 | 41.0 ± 45 |
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.
| Participants | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin |
|---|---|---|
| Number of Participants With Anti-Ramucirumab Antibodies | 1 | 3 |
Collected over Up to 31 Months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ramucirumab + S-1 + Oxaliplatin - Part A | 2/96 (2.1%) | 29/96 (30.2%) | 95/96 (99%) |
| Placebo + S-1 + Oxaliplatin - Part A | 1/93 (1.1%) | 24/93 (25.8%) | 93/93 (100%) |
| Ramucirumab + S-1 + Oxaliplatin Part B | 1/58 (1.7%) | 16/58 (27.6%) | 58/58 (100%) |
| Placebo + S-1 + Oxaliplatin - Part B | 0/64 (0%) | 14/64 (21.9%) | 64/64 (100%) |
| Event | Ramucirumab + S-1 + Oxaliplatin - Part A | Placebo + S-1 + Oxaliplatin - Part A | Ramucirumab + S-1 + Oxaliplatin Part B | Placebo + S-1 + Oxaliplatin - Part B |
|---|---|---|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 1/96 | 0/93 | 3/58 | 4/64 |
| Gastric perforationGastrointestinal disorders | 1/96 | 1/93 | 3/58 | 0/64 |
| PyelonephritisInfections and infestations | 0/96 | 0/93 | 2/58 | 0/64 |
| Abdominal painGastrointestinal disorders | 1/96 | 3/93 | 1/58 | 0/64 |
| Upper gastrointestinal haemorrhageGastrointestinal disorders | 3/96 | 0/93 | 0/58 | 1/64 |
| VomitingGastrointestinal disorders | 3/96 | 2/93 | 0/58 | 1/64 |
| AnaemiaBlood and lymphatic system disorders | 0/96 | 2/93 | 0/58 | 0/64 |
| EnterocolitisGastrointestinal disorders | 0/96 | 2/93 | 0/58 | 0/64 |
| Gastric stenosisGastrointestinal disorders | 0/96 | 2/93 | 0/58 | 0/64 |
| DiarrhoeaGastrointestinal disorders | 2/96 | 0/93 | 0/58 | 0/64 |
| Event | Ramucirumab + S-1 + Oxaliplatin - Part A | Placebo + S-1 + Oxaliplatin - Part A | Ramucirumab + S-1 + Oxaliplatin Part B | Placebo + S-1 + Oxaliplatin - Part B |
|---|---|---|---|---|
| Peripheral sensory neuropathyNervous system disorders | 56/96 | 70/93 | 8/58 | 14/64 |
| Decreased appetiteMetabolism and nutrition disorders | 53/96 | 57/93 | 9/58 | 12/64 |
| Neutrophil count decreasedInvestigations | 48/96 | 32/93 | 33/58 | 36/64 |
| NauseaGastrointestinal disorders | 54/96 | 37/93 | 5/58 | 4/64 |
| DiarrhoeaGastrointestinal disorders | 49/96 | 28/93 | 10/58 | 8/64 |
| AlopeciaSkin and subcutaneous tissue disorders | 10/96 | 2/93 | 26/58 | 30/64 |
| White blood cell count decreasedInvestigations | 24/96 | 18/93 | 19/58 | 24/64 |
| ConstipationGastrointestinal disorders | 33/96 | 30/93 | 3/58 | 6/64 |
| Platelet count decreasedInvestigations | 33/96 | 28/93 | 4/58 | 4/64 |
| VomitingGastrointestinal disorders | 28/96 | 21/93 | 5/58 | 7/64 |
All randomized participants who received any quantity of study drug.
| Age, Continuous(Years) | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin | Total |
|---|---|---|---|
| Mean | 59.2 ± 12.35 | 61.3 ± 11.53 | 60.2 ± 11.97 |
| Sex: Female, Male(Participants) | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin | Total |
|---|---|---|---|
| Female | 39 | 29 | 68 |
| Male | 57 | 64 | 121 |
| Ethnicity (NIH/OMB)(Participants) | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 0 | 0 | 0 |
| Unknown or Not Reported | 96 | 93 | 189 |
| Race (NIH/OMB)(Participants) | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 96 | 93 | 189 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Ramucirumab + S-1 + Oxaliplatin | Placebo + S-1 + Oxaliplatin | Total |
|---|---|---|---|
| South Korea | 20 | 20 | 40 |
| Japan | 65 | 64 | 129 |
| Taiwan | 11 | 9 | 20 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting information: Study protocol, Sap, Csr
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