Trial Outcomes & Findings for A Study in Participants With Advanced Solid Tumors (NCT NCT01682135)
NCT ID: NCT01682135
Last Updated: 2016-08-26
Results Overview
A summary of AEs and SAEs considered by the investigator to be drug-related is located in the Reported Adverse Events module. An AE is summarized if the onset date is on or after the first dose of study drug and within 30 days after the last dose, or it occurred before the first dose of study drug and worsened while on the therapy.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
28 participants
Primary outcome timeframe
Baseline through Study Completion (Up to 12 Weeks)
Results posted on
2016-08-26
Participant Flow
Participant study completion is defined as a participant either completing all 6 cycles of study drug or discontinuing study drug due to dose-limiting toxicities (DLT), then completing all required End-of-Therapy and End-of-Study assessments.
Participant milestones
| Measure |
Cohort 1 - 6 mg/kg/2w Ramucirumab
6 milligram per kilogram (mg/kg) ramucirumab administered intravenously (IV) every 2 weeks (w) for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2. After Cycle 1 treatment, participants who had an objective response or stable disease were permitted to receive ramucirumab at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.
|
Cohort 2 - 10 mg/kg/3w Ramucirumab
10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3. After Cycle 1 treatment, participants who had an objective response or stable disease were permitted to receive ramucirumab at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.
|
Cohort 3 - 8 mg/kg/2w Ramucirumab
8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). After Cycle 1 treatment, participants who had an objective response or stable disease were permitted to receive ramucirumab at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
10
|
12
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
6
|
10
|
12
|
|
Overall Study
COMPLETED
|
6
|
10
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study in Participants With Advanced Solid Tumors
Baseline characteristics by cohort
| Measure |
Cohort 1 - 6 mg/kg/2w Ramucirumab
n=6 Participants
6 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle) followed by dose escalation to Cohort 2. When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.
|
Cohort 2 - 10 mg/kg/3w Ramucirumab
n=10 Participants
10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle) followed by dose escalation to Cohort 3. When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.
|
Cohort 3 - 8 mg/kg/2w Ramucirumab
n=12 Participants
8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
51.20 Years
STANDARD_DEVIATION 9.060 • n=93 Participants
|
52.92 Years
STANDARD_DEVIATION 9.509 • n=4 Participants
|
58.18 Years
STANDARD_DEVIATION 9.444 • n=27 Participants
|
54.80 Years
STANDARD_DEVIATION 9.536 • n=483 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
14 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
14 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
28 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Region of Enrollment
China
|
6 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
28 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline through Study Completion (Up to 12 Weeks)Population: All enrolled participants who received at least one dose of study drug.
A summary of AEs and SAEs considered by the investigator to be drug-related is located in the Reported Adverse Events module. An AE is summarized if the onset date is on or after the first dose of study drug and within 30 days after the last dose, or it occurred before the first dose of study drug and worsened while on the therapy.
Outcome measures
| Measure |
Cohort 1: 6 mg/kg/2w Ramucirumab
n=6 Participants
6 mg/kg ramucirumab administered intravenously (IV) every 2 weeks (w) for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.
|
Cohort 2: 10 mg/kg/3w Ramucirumab
n=10 Participants
10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.
|
Cohort 3: 8 mg/kg/2w Ramucirumab
n=12 Participants
8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).
|
|---|---|---|---|
|
Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs)
Drug-Related Adverse Event
|
4 Participants
|
8 Participants
|
10 Participants
|
|
Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs)
Serious Adverse Event
|
0 Participants
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 & 2: Predose, End of Infusion, 0.5 hour (h) ,1h, 2h, 4h, 8h, 24h, 48h,72h or 96h, 168h, 264h, and 336h Postdose (and 504h Postdose Cohort 2 only)Population: All enrolled participants who received at least one dose of study drug and had evaluable Cmax pharmacokinetics (PK) data.
Outcome measures
| Measure |
Cohort 1: 6 mg/kg/2w Ramucirumab
n=6 Participants
6 mg/kg ramucirumab administered intravenously (IV) every 2 weeks (w) for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.
|
Cohort 2: 10 mg/kg/3w Ramucirumab
n=9 Participants
10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.
|
Cohort 3: 8 mg/kg/2w Ramucirumab
n=12 Participants
8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).
|
|---|---|---|---|
|
Pharmacokinetics: Maximum Concentration (Cmax) of Ramucirumab
Cycle 1 (n = 6, 9, 12)
|
155 microgram/milliliter (µg/mL)
Geometric Coefficient of Variation 13
|
186 microgram/milliliter (µg/mL)
Geometric Coefficient of Variation 22
|
190 microgram/milliliter (µg/mL)
Geometric Coefficient of Variation 39
|
|
Pharmacokinetics: Maximum Concentration (Cmax) of Ramucirumab
Cycle 2 (n = 1, 6, 8)
|
NA microgram/milliliter (µg/mL)
Geometric Coefficient of Variation NA
Geometric Mean and %CV not calculated for 1 participant. Individual Value = 155 µg/mL.
|
219 microgram/milliliter (µg/mL)
Geometric Coefficient of Variation 22
|
239 microgram/milliliter (µg/mL)
Geometric Coefficient of Variation 19
|
PRIMARY outcome
Timeframe: Cycle 2-5: PredosePopulation: All enrolled participants who received at least one dose of study drug and had evaluable Cmin PK data.
Outcome measures
| Measure |
Cohort 1: 6 mg/kg/2w Ramucirumab
n=5 Participants
6 mg/kg ramucirumab administered intravenously (IV) every 2 weeks (w) for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.
|
Cohort 2: 10 mg/kg/3w Ramucirumab
n=8 Participants
10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.
|
Cohort 3: 8 mg/kg/2w Ramucirumab
n=10 Participants
8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).
|
|---|---|---|---|
|
Pharmacokinetics: Minimum Concentration (Cmin) of Ramucirumab
Cycle 5 (n = 0, 3, 4)
|
NA µg/mL
Geometric Coefficient of Variation NA
Geometric Mean and %CV not calculated for 0 participants; no data.
|
56.5 µg/mL
Geometric Coefficient of Variation 17
|
92.5 µg/mL
Geometric Coefficient of Variation 19
|
|
Pharmacokinetics: Minimum Concentration (Cmin) of Ramucirumab
Cycle 2 (n = 5, 8, 10)
|
36.9 µg/mL
Geometric Coefficient of Variation 35
|
29.5 µg/mL
Geometric Coefficient of Variation 90
|
59.7 µg/mL
Geometric Coefficient of Variation 26
|
|
Pharmacokinetics: Minimum Concentration (Cmin) of Ramucirumab
Cycle 3 (n = 1, 2, 5)
|
NA µg/mL
Geometric Coefficient of Variation NA
Geometric Mean and %CV not calculated for 1 participant. Individual Value = 37.1 µg/mL.
|
NA µg/mL
Geometric Coefficient of Variation NA
Geometric Mean and %CV not calculated for 2 participants. Individual Values = 41.2 and 50.2 µg/mL.
|
68.7 µg/mL
Geometric Coefficient of Variation 28
|
|
Pharmacokinetics: Minimum Concentration (Cmin) of Ramucirumab
Cycle 4 (n = 1, 2, 4)
|
NA µg/mL
Geometric Coefficient of Variation NA
Geometric Mean and %CV not calculated for 1 participant. Individual Value = 51.9 µg/mL.
|
NA µg/mL
Geometric Coefficient of Variation NA
Geometric Mean and %CV not calculated for 2 participants. Individual Values = 56.0 and 84.1 µg/mL.
|
79.6 µg/mL
Geometric Coefficient of Variation 26
|
PRIMARY outcome
Timeframe: Cycle 1 & 2: Predose, End of Infusion, 0.5 hour (h) ,1h, 2h, 4h, 8h, 24h, 48h,72h or 96h, 168h, 264h, and 336h Postdose (and 504h Postdose Cohort 2 only)Population: All enrolled participants who received at least one dose of study drug and had evaluable AUC(0-∞) for Cycle 1 and AUC(τ,ss) for Cycle 2 PK data.
Cycle 1 analysis performed: Area Under the Concentration-Time Curve Zero to Infinity (AUC\[0-∞\]); Cycle 2 analysis performed: Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUC\[τ,ss\])
Outcome measures
| Measure |
Cohort 1: 6 mg/kg/2w Ramucirumab
n=5 Participants
6 mg/kg ramucirumab administered intravenously (IV) every 2 weeks (w) for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.
|
Cohort 2: 10 mg/kg/3w Ramucirumab
n=7 Participants
10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.
|
Cohort 3: 8 mg/kg/2w Ramucirumab
n=7 Participants
8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).
|
|---|---|---|---|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab
Cycle 1 AUC(0-∞) (n = 5, 7, 7)
|
870 Microgram*day/milliliter (µg*day/mL)
Geometric Coefficient of Variation 14
|
1430 Microgram*day/milliliter (µg*day/mL)
Geometric Coefficient of Variation 31
|
1350 Microgram*day/milliliter (µg*day/mL)
Geometric Coefficient of Variation 9
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab
Cycle 2 AUC(τ,ss) (n = 1, 6, 8)
|
NA Microgram*day/milliliter (µg*day/mL)
Geometric Coefficient of Variation NA
Geometric Mean and %CV not calculated for 1 participant. Mean Value = 892 µg\*day/mL).
|
1630 Microgram*day/milliliter (µg*day/mL)
Geometric Coefficient of Variation 32
|
1540 Microgram*day/milliliter (µg*day/mL)
Geometric Coefficient of Variation 16
|
SECONDARY outcome
Timeframe: Time Between Meeting Response Criteria and Progressive Disease or Death Due to Any Cause (Up to 10 Weeks)Population: All enrolled participants who received at least one dose of study drug. There were no participants censored due to no CR or PR responses.
Participants achieved an objective response if they had a best overall response of complete response (CR) or partial response (PR). 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 nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); 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. For each participant who is not known to have died or to have had objective progression of disease as of the data-inclusion cut-off date for a particular analysis, duration of tumor response was to be censored at the date of the participant's last objective tumor assessment prior to that cut-off date.
Outcome measures
| Measure |
Cohort 1: 6 mg/kg/2w Ramucirumab
n=6 Participants
6 mg/kg ramucirumab administered intravenously (IV) every 2 weeks (w) for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.
|
Cohort 2: 10 mg/kg/3w Ramucirumab
n=10 Participants
10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.
|
Cohort 3: 8 mg/kg/2w Ramucirumab
n=12 Participants
8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).
|
|---|---|---|---|
|
Duration of Response
|
0 Months
Interval 0.0 to 0.0
|
0 Months
Interval 0.0 to 0.0
|
0 Months
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline to Progressive Disease or Death Due to Any Cause (Up to 10 Weeks)Population: All enrolled participants who received at least one dose of study drug and had evaluable SD data. Participants censored for Cohort 1, 2, and 3: 3, 2, and 1, respectively.
Duration of SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. SD is measured at the start of the study drug until progressive disease or death due to any cause, whichever is first. Censoring occurred if a participant did not have a complete baseline disease assessment, initiated on another anti-cancer therapy (censored at the date of the last complete objective progression-free disease assessment before initiation of the new therapy), was not known to have died or had objective progression as of the data inclusion cutoff date for analysis.
Outcome measures
| Measure |
Cohort 1: 6 mg/kg/2w Ramucirumab
n=3 Participants
6 mg/kg ramucirumab administered intravenously (IV) every 2 weeks (w) for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.
|
Cohort 2: 10 mg/kg/3w Ramucirumab
n=7 Participants
10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.
|
Cohort 3: 8 mg/kg/2w Ramucirumab
n=8 Participants
8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).
|
|---|---|---|---|
|
Duration of Stable Disease (SD)
|
NA Months
The number of values in this cohort was too small to calculate due to censoring.
|
5.68 Months
Interval 2.79 to 12.22
|
5.29 Months
Interval 2.92 to 6.87
|
SECONDARY outcome
Timeframe: Baseline to Progressive Disease (Up to 10 Weeks)Population: All enrolled participants who received at least one dose of study drug. Censoring for Cohort 1, 2 and 3: 3, 2 and 2, respectively.
Time to progressive disease was measured from the start of study drug until progressive disease. Censoring occurred if a participant did not have a complete baseline disease assessment, initiated on another anti-cancer therapy (censored at the date of the last complete objective progression-free disease assessment before initiation of the new therapy), was not known to have died or had objective progression as of the data inclusion cutoff date for analysis.
Outcome measures
| Measure |
Cohort 1: 6 mg/kg/2w Ramucirumab
n=6 Participants
6 mg/kg ramucirumab administered intravenously (IV) every 2 weeks (w) for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.
|
Cohort 2: 10 mg/kg/3w Ramucirumab
n=10 Participants
10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.
|
Cohort 3: 8 mg/kg/2w Ramucirumab
n=12 Participants
8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).
|
|---|---|---|---|
|
Time to Disease Progression
|
1.41 Months
Interval 1.35 to
The number of values in this cohort was too small to calculate due to censoring.
|
3.38 Months
Interval 1.28 to 8.21
|
3.94 Months
Interval 1.22 to 5.55
|
SECONDARY outcome
Timeframe: Cycle 1: Pre-infusion, Cycle 2: Pre-infusion, Cycle 3: Pre-infusionPopulation: 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 |
Cohort 1: 6 mg/kg/2w Ramucirumab
n=6 Participants
6 mg/kg ramucirumab administered intravenously (IV) every 2 weeks (w) for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.
|
Cohort 2: 10 mg/kg/3w Ramucirumab
n=10 Participants
10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.
|
Cohort 3: 8 mg/kg/2w Ramucirumab
n=12 Participants
8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).
|
|---|---|---|---|
|
Number of Participants With Anti-Ramucirumab Antibodies
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline to Progressive Disease or Participant Stopped Study (Up to 10 Weeks)Population: All enrolled participants who received at least one dose of study drug.
Participants achieved disease control if they had a BOR of CR, PR or SD. Progressive Disease (PD) and those participants which were Not Evaluable (NE) were also reported. 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 nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); 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.
Outcome measures
| Measure |
Cohort 1: 6 mg/kg/2w Ramucirumab
n=6 Participants
6 mg/kg ramucirumab administered intravenously (IV) every 2 weeks (w) for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.
|
Cohort 2: 10 mg/kg/3w Ramucirumab
n=10 Participants
10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.
|
Cohort 3: 8 mg/kg/2w Ramucirumab
n=12 Participants
8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).
|
|---|---|---|---|
|
Number of Participants With Best Objective Response (BOR)
Complete Response (CR)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Best Objective Response (BOR)
Partial Response (PR)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Best Objective Response (BOR)
Stable Disease (SD)
|
3 Participants
|
7 Participants
|
8 Participants
|
|
Number of Participants With Best Objective Response (BOR)
Progressive Disease (PD)
|
3 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Best Objective Response (BOR)
Not Evaluable (NE)
|
0 Participants
|
0 Participants
|
1 Participants
|
Adverse Events
Cohort 1 - 6mg/kg/2w Ramucirumab
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort 2 - 10mg/kg/3w Ramucirumab
Serious events: 2 serious events
Other events: 10 other events
Deaths: 0 deaths
Cohort 3 - 8mg/kg/2w Ramucirumab
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1 - 6mg/kg/2w Ramucirumab
n=6 participants at risk
6mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.
|
Cohort 2 - 10mg/kg/3w Ramucirumab
n=10 participants at risk
10mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.
|
Cohort 3 - 8mg/kg/2w Ramucirumab
n=12 participants at risk
8mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).
|
|---|---|---|---|
|
Gastrointestinal disorders
Impaired gastric emptying
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 2
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
General disorders
Fatigue
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/12
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
Other adverse events
| Measure |
Cohort 1 - 6mg/kg/2w Ramucirumab
n=6 participants at risk
6mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.
|
Cohort 2 - 10mg/kg/3w Ramucirumab
n=10 participants at risk
10mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.
|
Cohort 3 - 8mg/kg/2w Ramucirumab
n=12 participants at risk
8mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
33.3%
2/6 • Number of events 4
|
10.0%
1/10 • Number of events 2
|
16.7%
2/12 • Number of events 2
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Cardiac disorders
Extrasystoles
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/12
|
|
Cardiac disorders
Palpitations
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/12
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/6
|
30.0%
3/10 • Number of events 27
|
33.3%
4/12 • Number of events 10
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/6
|
30.0%
3/10 • Number of events 3
|
0.00%
0/12
|
|
Cardiac disorders
Ventricular arrhythmia
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Ear and labyrinth disorders
Tinnitus
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/12
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Eye disorders
Vision blurred
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/6
|
20.0%
2/10 • Number of events 2
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
2/6 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
16.7%
2/12 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Gastrointestinal disorders
Constipation
|
50.0%
3/6 • Number of events 4
|
10.0%
1/10 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6 • Number of events 2
|
0.00%
0/10
|
25.0%
3/12 • Number of events 8
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.00%
0/6
|
10.0%
1/10 • Number of events 3
|
0.00%
0/12
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.00%
0/6
|
10.0%
1/10 • Number of events 2
|
0.00%
0/12
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Gastrointestinal disorders
Gingival pain
|
0.00%
0/6
|
20.0%
2/10 • Number of events 2
|
0.00%
0/12
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
16.7%
1/6 • Number of events 1
|
30.0%
3/10 • Number of events 3
|
16.7%
2/12 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6
|
30.0%
3/10 • Number of events 3
|
8.3%
1/12 • Number of events 3
|
|
Gastrointestinal disorders
Oral dysaesthesia
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/6
|
20.0%
2/10 • Number of events 2
|
16.7%
2/12 • Number of events 2
|
|
Gastrointestinal disorders
Stomatitis
|
33.3%
2/6 • Number of events 2
|
20.0%
2/10 • Number of events 2
|
0.00%
0/12
|
|
Gastrointestinal disorders
Toothache
|
33.3%
2/6 • Number of events 2
|
0.00%
0/10
|
0.00%
0/12
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
2/6 • Number of events 3
|
40.0%
4/10 • Number of events 9
|
16.7%
2/12 • Number of events 3
|
|
General disorders
Chills
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
General disorders
Face oedema
|
33.3%
2/6 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
16.7%
2/12 • Number of events 2
|
|
General disorders
Facial pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/12
|
|
General disorders
Fatigue
|
100.0%
6/6 • Number of events 8
|
80.0%
8/10 • Number of events 11
|
41.7%
5/12 • Number of events 5
|
|
General disorders
Influenza like illness
|
0.00%
0/6
|
20.0%
2/10 • Number of events 2
|
25.0%
3/12 • Number of events 4
|
|
General disorders
Non-cardiac chest pain
|
16.7%
1/6 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
33.3%
4/12 • Number of events 5
|
|
General disorders
Oedema peripheral
|
16.7%
1/6 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
25.0%
3/12 • Number of events 3
|
|
General disorders
Pyrexia
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
|
Hepatobiliary disorders
Gallbladder pain
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Hepatobiliary disorders
Hepatic pain
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
16.7%
2/12 • Number of events 2
|
|
Immune system disorders
Contrast media allergy
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Infections and infestations
Conjunctivitis
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/12
|
|
Infections and infestations
Vaginal infection
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/7
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
2/6 • Number of events 2
|
50.0%
5/10 • Number of events 9
|
41.7%
5/12 • Number of events 11
|
|
Investigations
Amylase increased
|
0.00%
0/6
|
0.00%
0/10
|
16.7%
2/12 • Number of events 3
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
2/6 • Number of events 2
|
50.0%
5/10 • Number of events 8
|
58.3%
7/12 • Number of events 13
|
|
Investigations
Blood alkaline phosphatase increased
|
16.7%
1/6 • Number of events 1
|
20.0%
2/10 • Number of events 2
|
0.00%
0/12
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Investigations
Blood creatinine increased
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Investigations
Electrocardiogram st segment abnormal
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Electrocardiogram t wave abnormal
|
0.00%
0/6
|
30.0%
3/10 • Number of events 5
|
0.00%
0/12
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Glucose urine present
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Investigations
Neutrophil count decreased
|
16.7%
1/6 • Number of events 1
|
40.0%
4/10 • Number of events 8
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Platelet count decreased
|
16.7%
1/6 • Number of events 2
|
40.0%
4/10 • Number of events 4
|
8.3%
1/12 • Number of events 2
|
|
Investigations
Red blood cell count decreased
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Weight decreased
|
16.7%
1/6 • Number of events 1
|
20.0%
2/10 • Number of events 2
|
25.0%
3/12 • Number of events 4
|
|
Investigations
White blood cell count decreased
|
33.3%
2/6 • Number of events 3
|
30.0%
3/10 • Number of events 7
|
0.00%
0/12
|
|
Investigations
White blood cells urine positive
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Metabolism and nutrition disorders
Decreased appetite
|
33.3%
2/6 • Number of events 2
|
50.0%
5/10 • Number of events 5
|
25.0%
3/12 • Number of events 4
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
16.7%
1/6 • Number of events 2
|
30.0%
3/10 • Number of events 3
|
8.3%
1/12 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/6
|
0.00%
0/10
|
16.7%
2/12 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
16.7%
1/6 • Number of events 1
|
30.0%
3/10 • Number of events 5
|
0.00%
0/12
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
33.3%
2/6 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
1/6 • Number of events 1
|
30.0%
3/10 • Number of events 4
|
16.7%
2/12 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
16.7%
1/6 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
16.7%
1/6 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/6
|
0.00%
0/10
|
25.0%
3/12 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
33.3%
2/6 • Number of events 2
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6
|
0.00%
0/10
|
25.0%
3/12 • Number of events 4
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
50.0%
3/6 • Number of events 3
|
10.0%
1/10 • Number of events 1
|
25.0%
3/12 • Number of events 4
|
|
Nervous system disorders
Headache
|
16.7%
1/6 • Number of events 2
|
20.0%
2/10 • Number of events 3
|
33.3%
4/12 • Number of events 7
|
|
Nervous system disorders
Hemiparesis
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/12
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/6
|
0.00%
0/10
|
16.7%
2/12 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
16.7%
1/6 • Number of events 1
|
20.0%
2/10 • Number of events 2
|
0.00%
0/12
|
|
Renal and urinary disorders
Haematuria
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/12
|
|
Renal and urinary disorders
Proteinuria
|
50.0%
3/6 • Number of events 8
|
30.0%
3/10 • Number of events 5
|
50.0%
6/12 • Number of events 8
|
|
Renal and urinary disorders
Renal failure chronic
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Renal and urinary disorders
Urinary tract obstruction
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/12
|
|
Renal and urinary disorders
Urinary tract pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/12
|
|
Reproductive system and breast disorders
Menstruation irregular
|
0.00%
0/4
|
33.3%
1/3 • Number of events 2
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • Number of events 1
|
20.0%
2/10 • Number of events 2
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/6
|
10.0%
1/10 • Number of events 2
|
16.7%
2/12 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
50.0%
3/6 • Number of events 3
|
20.0%
2/10 • Number of events 2
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
50.0%
3/6 • Number of events 3
|
30.0%
3/10 • Number of events 6
|
8.3%
1/12 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/6
|
20.0%
2/10 • Number of events 2
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
0.00%
0/6
|
0.00%
0/10
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/6
|
10.0%
1/10 • Number of events 1
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
16.7%
1/6 • Number of events 1
|
0.00%
0/10
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/6
|
20.0%
2/10 • Number of events 2
|
0.00%
0/12
|
|
Vascular disorders
Hypertension
|
50.0%
3/6 • Number of events 8
|
70.0%
7/10 • Number of events 29
|
41.7%
5/12 • Number of events 14
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60