Trial Outcomes & Findings for A Study of Ramucirumab in Treating Japanese Participants With Metastatic Gastric or Gastroesophageal Junction Cancer (NCT NCT01983878)
NCT ID: NCT01983878
Last Updated: 2019-09-30
Results Overview
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.
COMPLETED
PHASE2
36 participants
12 Weeks
2019-09-30
Participant Flow
Participant study completion was defined as participant assessment at the 12-week visit or withdrawal from the study.
Participant milestones
| Measure |
Ramucirumab 8 mg/kg
Ramucirumab 8 milligrams per kilogram (mg/kg) administered intravenously (IV) once every 2 weeks. Treatment continued until there is evidence of progressive disease (PD), the development of unacceptable toxicity, protocol non-compliance, or withdrawal of consent.
|
|---|---|
|
Overall Study
STARTED
|
36
|
|
Overall Study
Received At Least One Dose of Study Drug
|
36
|
|
Overall Study
COMPLETED
|
36
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Ramucirumab in Treating Japanese Participants With Metastatic Gastric or Gastroesophageal Junction Cancer
Baseline characteristics by cohort
| Measure |
Ramucirumab 8 mg/kg
n=36 Participants
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.
|
|---|---|
|
Age, Continuous
|
66.7 Years
STANDARD_DEVIATION 9.75 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
36 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
36 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
36 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group performance status (ECOG PS) 0 vs. 1
Performance Status = 0
|
24 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group performance status (ECOG PS) 0 vs. 1
Performance Status = 1
|
12 Participants
n=5 Participants
|
|
Basis for Pathological Diagnosis
Histopathological
|
36 Participants
n=5 Participants
|
|
Basis for Pathological Diagnosis
Cytological
|
0 Participants
n=5 Participants
|
|
Pathological Diagnosis
Adenocarcinoma, Gastroesophageal Junction
|
1 Participants
n=5 Participants
|
|
Pathological Diagnosis
Adenocarcinoma, Gastric
|
35 Participants
n=5 Participants
|
|
Initial Tumor Location
Body of stomach
|
19 Participants
n=5 Participants
|
|
Initial Tumor Location
Gastric Cardia
|
3 Participants
n=5 Participants
|
|
Initial Tumor Location
Gastric, Antrum
|
14 Participants
n=5 Participants
|
|
Human Epidermal Growth Factor Receptor 2 (HER2) Status
Positive
|
6 Participants
n=5 Participants
|
|
Human Epidermal Growth Factor Receptor 2 (HER2) Status
Negative
|
26 Participants
n=5 Participants
|
|
Human Epidermal Growth Factor Receptor 2 (HER2) Status
Not Done
|
3 Participants
n=5 Participants
|
|
Human Epidermal Growth Factor Receptor 2 (HER2) Status
Unknown
|
1 Participants
n=5 Participants
|
|
Grade
Well-differentiated (Low grade)
|
4 Participants
n=5 Participants
|
|
Grade
Moderately differentiated (Intermediate grade)
|
11 Participants
n=5 Participants
|
|
Grade
Poorly differentiated (High grade)
|
20 Participants
n=5 Participants
|
|
Grade
Not Applicable
|
1 Participants
n=5 Participants
|
|
Histology
Intestinal
|
15 Participants
n=5 Participants
|
|
Histology
Diffuse
|
13 Participants
n=5 Participants
|
|
Histology
Mixed
|
5 Participants
n=5 Participants
|
|
Histology
Not Applicable
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 WeeksPopulation: Full Analysis Set (FAS): all enrolled participants who received at least one dose of the study drug. 8 participants were censored.
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.
Outcome measures
| Measure |
Ramucirumab 8 mg/kg
n=36 Participants
Ramucirumab 8 mg/kg administered IV once every 2 weeks. Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol non-compliance, or withdrawal of consent.
|
|---|---|
|
Percentage of Participants Who Are Progression-Free at 12 Weeks (Progression-Free Survival [PFS] Rate at 12 Weeks)
|
23.8 Percentage of Participants
Interval 12.4 to 37.2
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Ramucirumab 8 mg/kg
n=36 Participants
Ramucirumab 8 mg/kg administered IV once every 2 weeks. Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol non-compliance, or withdrawal of consent.
|
|---|---|
|
Progression-Free Survival (PFS)
|
6.6 Weeks
Interval 6.1 to 7.1
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Ramucirumab 8 mg/kg
n=36 Participants
Ramucirumab 8 mg/kg administered IV once every 2 weeks. Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol non-compliance, or withdrawal of consent.
|
|---|---|
|
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
|
0 Percentage of Participants
Interval 0.0 to 7.98
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Ramucirumab 8 mg/kg
n=36 Participants
Ramucirumab 8 mg/kg administered IV once every 2 weeks. Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol non-compliance, or withdrawal of consent.
|
|---|---|
|
Percentage of Participants Achieving Stable Disease (SD) or a Confirmed CR or PR [Disease Control Rate (DCR)]
|
30.6 Percentage of Participants
Interval 18.18 to 45.47
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Ramucirumab 8 mg/kg
n=36 Participants
Ramucirumab 8 mg/kg administered IV once every 2 weeks. Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol non-compliance, or withdrawal of consent.
|
|---|---|
|
Overall Survival (OS)
|
8.6 Months
Interval 5.7 to 10.7
|
SECONDARY outcome
Timeframe: Cycle 1: Pre-infusion, Cycle 2: Pre-infusion, Cycle 3: Pre-infusion, Follow UpPopulation: All enrolled participants who received at least one dose of study drug and had evaluable immunogenicity data.
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.
Outcome measures
| Measure |
Ramucirumab 8 mg/kg
n=36 Participants
Ramucirumab 8 mg/kg administered IV once every 2 weeks. Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol non-compliance, or withdrawal of consent.
|
|---|---|
|
Number of Participants With Anti-Ramucirumab Antibodies
|
1 participants
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1: Pre-Dose, End of Infusion. 1, 4, 23, 47, 95, 167, 263, and 335 Hours Post-DosePopulation: PK population: enrolled participants who received at least one dose of the study drug and had evaluable ramucirumab PK data.
Outcome measures
| Measure |
Ramucirumab 8 mg/kg
n=6 Participants
Ramucirumab 8 mg/kg administered IV once every 2 weeks. Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol non-compliance, or withdrawal of consent.
|
|---|---|
|
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab
|
161 micrograms/milliliter (μg/mL)
Geometric Coefficient of Variation 16.2
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1: Pre-Dose, End of Infusion: 1, 4, 23, 47, 95, 167, 263, and 335 Hours Post-DosePopulation: PK population: Enrolled participants who received at least one dose of the study drug and had evaluable ramucirumab PK data.
Outcome measures
| Measure |
Ramucirumab 8 mg/kg
n=6 Participants
Ramucirumab 8 mg/kg administered IV once every 2 weeks. Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol non-compliance, or withdrawal of consent.
|
|---|---|
|
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
|
Adverse Events
Ramucirumab 8 mg/kg
Serious adverse events
| Measure |
Ramucirumab 8 mg/kg
n=36 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Ileus
|
5.6%
2/36 • Number of events 3
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
5.6%
2/36 • Number of events 2
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
2.8%
1/36 • Number of events 1
|
|
Infections and infestations
Device related infection
|
2.8%
1/36 • Number of events 1
|
|
Vascular disorders
Hypertension
|
2.8%
1/36 • Number of events 1
|
Other adverse events
| Measure |
Ramucirumab 8 mg/kg
n=36 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
5.6%
2/36 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain
|
13.9%
5/36 • Number of events 5
|
|
Gastrointestinal disorders
Ascites
|
5.6%
2/36 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
9/36 • Number of events 16
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.6%
2/36 • Number of events 2
|
|
Gastrointestinal disorders
Ileus
|
5.6%
2/36 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
8.3%
3/36 • Number of events 5
|
|
Gastrointestinal disorders
Stomatitis
|
5.6%
2/36 • Number of events 2
|
|
General disorders
Face oedema
|
8.3%
3/36 • Number of events 3
|
|
General disorders
Fatigue
|
8.3%
3/36 • Number of events 5
|
|
General disorders
Malaise
|
16.7%
6/36 • Number of events 6
|
|
General disorders
Oedema
|
5.6%
2/36 • Number of events 2
|
|
General disorders
Oedema peripheral
|
13.9%
5/36 • Number of events 5
|
|
General disorders
Pyrexia
|
11.1%
4/36 • Number of events 4
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
5.6%
2/36 • Number of events 2
|
|
Infections and infestations
Nasopharyngitis
|
5.6%
2/36 • Number of events 3
|
|
Infections and infestations
Upper respiratory tract infection
|
5.6%
2/36 • Number of events 2
|
|
Investigations
Neutrophil count decreased
|
8.3%
3/36 • Number of events 5
|
|
Investigations
Platelet count decreased
|
11.1%
4/36 • Number of events 4
|
|
Investigations
White blood cell count decreased
|
8.3%
3/36 • Number of events 3
|
|
Metabolism and nutrition disorders
Decreased appetite
|
22.2%
8/36 • Number of events 8
|
|
Metabolism and nutrition disorders
Dehydration
|
5.6%
2/36 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
5.6%
2/36 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
5.6%
2/36 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.6%
2/36 • Number of events 2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
5.6%
2/36 • Number of events 2
|
|
Nervous system disorders
Headache
|
8.3%
3/36 • Number of events 4
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
5.6%
2/36 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
5.6%
2/36 • Number of events 2
|
|
Renal and urinary disorders
Haematuria
|
5.6%
2/36 • Number of events 2
|
|
Renal and urinary disorders
Proteinuria
|
19.4%
7/36 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
8.3%
3/36 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
8.3%
3/36 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.6%
2/36 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.6%
2/36 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
5.6%
2/36 • Number of events 2
|
|
Vascular disorders
Hypertension
|
25.0%
9/36 • Number of events 9
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60