Gastric Cancer
Conditions
Brief summary
The purpose of this study is to evaluate progression-free survival in participants with gastric or gastroesophageal junction cancer who have had disease progression following first-line therapy who undergo treatment with ramucirumab.
Interventions
DRUGRamucirumab
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed gastric carcinoma, including gastric adenocarcinoma or Gastroesophageal Junction (GEJ) adenocarcinoma * Metastatic disease or locally recurrent, unresectable disease * Measurable disease and/or evaluable disease * Experienced disease progression during or within 4 months after the last dose of first-line therapy for metastatic disease, or during or within 6 months after the last dose of adjuvant therapy * Life expectancy of at least 3 months * Resolution to Grade less than or equal to 1 by the National Cancer Institute Common Terminology Criteria for Adverse , Version 4.03, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy * Eastern Cooperative Oncology Group performance status score of 0-1 * Has adequate organ function * Must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods), if sexually active * Female participants of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment
Exclusion criteria
* Documented and/or symptomatic brain or leptomeningeal metastases * Bone metastases * Experienced Grade 3/4 gastrointestinal (GI) bleeding within 3 months prior to enrollment * Experienced any arterial thromboembolic event within 6 months prior to enrollment * Ongoing or active significant infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thromboembolic or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the opinion of the investigator * Ongoing or active psychiatric illness or social situation that would limit compliance with study requirements * Blood pressure in abnormal range despite standard medical management * Has a serious or nonhealing wound, ulcer, or bone fracture * Received chemotherapy, radiotherapy, immunotherapy, or targeted therapy for gastric cancer * Received any investigational therapy within 30 days prior to enrollment * Undergone major surgery within 28 days prior to enrollment, or subcutaneous venous access device placement within 7 days prior to enrollment * Received prior therapy with an agent that directly inhibits vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor 2 (VEGFR-2) activity (including bevacizumab), or any anti-angiogenic agent * Receiving chronic therapy with nonsteroidal anti-inflammatory drugs or receiving other antiplatelet agents. Aspirin use at doses up to 325 milligrams per day is permitted * Has elective or planned major surgery to be performed during the course of the clinical study * Has a known allergy to any of the treatment components * Pregnant or breastfeeding * Have positive test results for human immunodeficiency virus, hepatitis B, or hepatitis C antibodies * Known alcohol or drug dependency * Previous or concurrent malignancy except for basal or squamous cell skin cancer (nonmelanoma) and/or pre-invasive carcinoma of the cervix, mucosal gastrointestinal or uterine carcinoma, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to enrollment * Currently enrolled in a clinical trial involving an investigational product or non-approved use of a drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Are Progression-Free at 12 Weeks (Progression-Free Survival [PFS] Rate at 12 Weeks) | 12 Weeks | The 12-week PFS rate is the probability of participants who survived during the first 12 weeks in the study without disease progression. It was estimated using the Kaplan-Meier method for the main analysis of the 12-week PFS rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | Baseline to Measured PD or Death from Any Cause (Up to 38.0 Weeks) | Participants achieved an objective response if they had a best overall response of CR or PR. According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels \[if tumor markers were initially above the upper limit of normal (ULN)\]. The percentage of participants who achieved an objective response = (number of participants with CR or PR)/(number of participants assessed)\*100. |
| Percentage of Participants Achieving Stable Disease (SD) or a Confirmed CR or PR [Disease Control Rate (DCR)] | Baseline to Measured PD or Death from Any Cause (Up to 12 Months) | Participants achieved disease control if they had a best overall response of CR, PR or SD. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all non-target lesions, and the normalization of tumor marker levels (if tumor markers were initially above the ULN); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. The percentage of participants who achieved disease control = (number of participants with CR, PR, or SD)/(number of participants assessed)\*100. |
| Overall Survival (OS) | Baseline to Death from Any Cause (Up to 13 Months) | The OS time is defined as the time from baseline to the date of death from any cause. If a participant is not known to have died on or before the date of data cut-off, OS data will be censored on the last date (on or before the cut-off date) the participant was known to be alive. |
| Progression-Free Survival (PFS) | Baseline to Measured PD or Death from Any Cause (Up to 30.3 weeks) | The time from baseline to measured Progressive Disease (PD) as defined by RECIST v.1.1 \[defined as \> 20% increase from smallest sum of longest diameter recorded since treatment started (best response)\], or death due to any cause, whichever is first. |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab | Cycle 1 Day 1: Pre-Dose, End of Infusion. 1, 4, 23, 47, 95, 167, 263, and 335 Hours Post-Dose | — |
| PK: Area Under the Curve Time Zero to Infinity (AUC[0-∞]) of Ramucirumab | Cycle 1 Day 1: Pre-Dose, End of Infusion: 1, 4, 23, 47, 95, 167, 263, and 335 Hours Post-Dose | — |
| Number of Participants With Anti-Ramucirumab Antibodies | Cycle 1: Pre-infusion, Cycle 2: Pre-infusion, Cycle 3: Pre-infusion, Follow Up | A sample will be considered positive for circulating anti-ramucirumab antibodies if it exhibits a post-baseline antibody level that exceeds the upper 95% confidence interval of the mean determined from the normal anti-ramucirumab level seen in healthy untreated individuals. A participant will be considered to have an anti-ramucirumab response if there are 2 consecutive positive samples or if the final sample tested is positive. |
Countries
Japan
Participant flow
Pre-assignment details
Participant study completion was defined as participant assessment at the 12-week visit or withdrawal from the study.
Participants by arm
| Arm | Count |
|---|---|
| Ramucirumab 8 mg/kg Ramucirumab 8 mg/kg administered IV once every 2 weeks. Treatment continued until there is evidence of PD, the development of unacceptable toxicity, protocol non-compliance, or withdrawal of consent. | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | Ramucirumab 8 mg/kg |
|---|---|
| Age, Continuous | 66.7 Years STANDARD_DEVIATION 9.75 |
| Basis for Pathological Diagnosis Cytological | 0 Participants |
| Basis for Pathological Diagnosis Histopathological | 36 Participants |
| Eastern Cooperative Oncology Group performance status (ECOG PS) 0 vs. 1 Performance Status = 0 | 24 Participants |
| Eastern Cooperative Oncology Group performance status (ECOG PS) 0 vs. 1 Performance Status = 1 | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Grade Moderately differentiated (Intermediate grade) | 11 Participants |
| Grade Not Applicable | 1 Participants |
| Grade Poorly differentiated (High grade) | 20 Participants |
| Grade Well-differentiated (Low grade) | 4 Participants |
| Histology Diffuse | 13 Participants |
| Histology Intestinal | 15 Participants |
| Histology Mixed | 5 Participants |
| Histology Not Applicable | 3 Participants |
| Human Epidermal Growth Factor Receptor 2 (HER2) Status Negative | 26 Participants |
| Human Epidermal Growth Factor Receptor 2 (HER2) Status Not Done | 3 Participants |
| Human Epidermal Growth Factor Receptor 2 (HER2) Status Positive | 6 Participants |
| Human Epidermal Growth Factor Receptor 2 (HER2) Status Unknown | 1 Participants |
| Initial Tumor Location Body of stomach | 19 Participants |
| Initial Tumor Location Gastric, Antrum | 14 Participants |
| Initial Tumor Location Gastric Cardia | 3 Participants |
| Pathological Diagnosis Adenocarcinoma, Gastric | 35 Participants |
| Pathological Diagnosis Adenocarcinoma, Gastroesophageal Junction | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 36 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 36 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 35 / 36 |
| serious Total, serious adverse events | 7 / 36 |
Outcome results
Primary
Percentage of Participants Who Are Progression-Free at 12 Weeks (Progression-Free Survival [PFS] Rate at 12 Weeks)
The 12-week PFS rate is the probability of participants who survived during the first 12 weeks in the study without disease progression. It was estimated using the Kaplan-Meier method for the main analysis of the 12-week PFS rate.
Time frame: 12 Weeks
Population: Full Analysis Set (FAS): all enrolled participants who received at least one dose of the study drug. 8 participants were censored.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramucirumab 8 mg/kg | Percentage of Participants Who Are Progression-Free at 12 Weeks (Progression-Free Survival [PFS] Rate at 12 Weeks) | 23.8 Percentage of Participants |
Secondary
Number of Participants With Anti-Ramucirumab Antibodies
A sample will be considered positive for circulating anti-ramucirumab antibodies if it exhibits a post-baseline antibody level that exceeds the upper 95% confidence interval of the mean determined from the normal anti-ramucirumab level seen in healthy untreated individuals. A participant will be considered to have an anti-ramucirumab response if there are 2 consecutive positive samples or if the final sample tested is positive.
Time frame: Cycle 1: Pre-infusion, Cycle 2: Pre-infusion, Cycle 3: Pre-infusion, Follow Up
Population: All enrolled participants who received at least one dose of study drug and had evaluable immunogenicity data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramucirumab 8 mg/kg | Number of Participants With Anti-Ramucirumab Antibodies | 1 participants |
Secondary
Overall Survival (OS)
The OS time is defined as the time from baseline to the date of death from any cause. If a participant is not known to have died on or before the date of data cut-off, OS data will be censored on the last date (on or before the cut-off date) the participant was known to be alive.
Time frame: Baseline to Death from Any Cause (Up to 13 Months)
Population: FAS: all enrolled participants who received at least one dose of the study drug. 18 participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramucirumab 8 mg/kg | Overall Survival (OS) | 8.6 Months |
Secondary
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Participants achieved an objective response if they had a best overall response of CR or PR. According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels \[if tumor markers were initially above the upper limit of normal (ULN)\]. The percentage of participants who achieved an objective response = (number of participants with CR or PR)/(number of participants assessed)\*100.
Time frame: Baseline to Measured PD or Death from Any Cause (Up to 38.0 Weeks)
Population: FAS: all enrolled participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramucirumab 8 mg/kg | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | 0 Percentage of Participants |
Secondary
Percentage of Participants Achieving Stable Disease (SD) or a Confirmed CR or PR [Disease Control Rate (DCR)]
Participants achieved disease control if they had a best overall response of CR, PR or SD. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all non-target lesions, and the normalization of tumor marker levels (if tumor markers were initially above the ULN); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. The percentage of participants who achieved disease control = (number of participants with CR, PR, or SD)/(number of participants assessed)\*100.
Time frame: Baseline to Measured PD or Death from Any Cause (Up to 12 Months)
Population: FAS: all enrolled participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramucirumab 8 mg/kg | Percentage of Participants Achieving Stable Disease (SD) or a Confirmed CR or PR [Disease Control Rate (DCR)] | 30.6 Percentage of Participants |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab
Time frame: Cycle 1 Day 1: Pre-Dose, End of Infusion. 1, 4, 23, 47, 95, 167, 263, and 335 Hours Post-Dose
Population: PK population: enrolled participants who received at least one dose of the study drug and had evaluable ramucirumab PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ramucirumab 8 mg/kg | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab | 161 micrograms/milliliter (μg/mL) | Geometric Coefficient of Variation 16.2 |
Secondary
PK: Area Under the Curve Time Zero to Infinity (AUC[0-∞]) of Ramucirumab
Time frame: Cycle 1 Day 1: Pre-Dose, End of Infusion: 1, 4, 23, 47, 95, 167, 263, and 335 Hours Post-Dose
Population: PK population: Enrolled participants who received at least one dose of the study drug and had evaluable ramucirumab PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ramucirumab 8 mg/kg | PK: Area Under the Curve Time Zero to Infinity (AUC[0-∞]) of Ramucirumab | 25600 hours x micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 34.2 |
Secondary
Progression-Free Survival (PFS)
The time from baseline to measured Progressive Disease (PD) as defined by RECIST v.1.1 \[defined as \> 20% increase from smallest sum of longest diameter recorded since treatment started (best response)\], or death due to any cause, whichever is first.
Time frame: Baseline to Measured PD or Death from Any Cause (Up to 30.3 weeks)
Population: FAS: all enrolled participants who received at least one dose of the study drug. 8 participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramucirumab 8 mg/kg | Progression-Free Survival (PFS) | 6.6 Weeks |