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Study of Icrucumab (IMC-18F1) or Ramucirumab Drug Product (DP) in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients

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ClinicalTrials.gov Identifier: NCT01234402
Recruitment Status : Completed
First Posted : November 4, 2010
Results First Posted : August 14, 2019
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Biological: Ramucirumab DP
Biological: IMC-18F1
Drug: Capecitabine
Enrollment 153
Recruitment Details Participants in Capecitabine arm were allowed to cross-over to ramucirumab or icrucumab in combination with capecitabine, after radiographic disease progression while on capecitabine.
Pre-assignment Details Completers are those participants who died or alive and on study at conclusion but off treatment.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine Capecitabine
Hide Arm/Group Description Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle. Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants received 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

After radiographic diseases progression while on Capecitabine, participants were crossed-over to either Ramucirumab or Icrucumab;

Participants crossed-over to Ramucirumab + Capecitabine had received 10 mg/kg Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants crossed-over to Icrucumab + Capecitabine received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Period Title: Overall Study
Started 52 51 50
Received at Least One Dose of Study Drug 52 49 49
Capecitabine Crossover to Ramucirumab 0 0 29
Capecitabine Crossover to Icrucumab 0 0 1
Completed 51 45 42
Not Completed 1 6 8
Reason Not Completed
Lost to Follow-up             0             1             3
Withdrawal by Subject             1             3             4
Never treated: Death             0             0             1
Never treated: Withdrawal By Subject             0             1             0
Never treated: Insurance Denied Xeloda             0             1             0
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine Capecitabine Total
Hide Arm/Group Description Participants received 10 mg/kg Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle. Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants received 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

After radiographic diseases progression while on Capecitabine, participants were crossed-over to either Ramucirumab or Icrucumab;

Participants crossed-over to Ramucirumab + Capecitabine had received 10 mg/kg Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants crossed-over to Icrucumab + Capecitabine received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

 Total of all reporting groups
Overall Number of Baseline Participants 52 49 49 150
Hide Baseline Analysis Population Description
All randomized participants who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 52 participants 49 participants 49 participants 150 participants
55.2  (10.75) 51.1  (11.54) 53.5  (11.12) 53.3  (11.19)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 49 participants 49 participants 150 participants
Female 52 48 49 149
Male 0 1 0 1
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 49 participants 49 participants 150 participants
Hispanic or Latino 2 3 1 6
Not Hispanic or Latino 49 44 45 138
Unknown or Not Reported 1 2 3 6
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 49 participants 49 participants 150 participants
American Indian or Alaska Native 0 1 0 1
American Indian or Alaska Native,White 0 0 1 1
Asian 2 1 1 4
Black or African American 13 8 4 25
Native Hawaiian or Other Pacific Islander 0 0 1 1
White 36 37 39 112
White, Other 0 0 1 1
Other 1 2 2 5
1.Primary Outcome
Title Progression-Free Survival (PFS)
Hide Description 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) and the appearance of ≥1 new lesions was progression. Participants who did not progress, were lost to follow-up, or had missed 2 or more scheduled tumor assessments were censored at the day of their last adequate tumor assessment.
Time Frame From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 97 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug; Censored participants: Ramucirumab + Capecitabine = 12; Icrucumab + Capecitabine = 11; Capecitabine = 7
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine Capecitabine
Hide Arm/Group Description:
Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants received 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

After radiographic diseases progression while on Capecitabine, participants were crossed-over to either Ramucirumab or Icrucumab;

Participants crossed-over to Ramucirumab + Capecitabine had received 10 mg/kg Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants crossed-over to Icrucumab + Capecitabine received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 52 49 49
Median (95% Confidence Interval)
Unit of Measure: Weeks
22.1
(12.1 to 36.1)
7.3
(6.3 to 13.0)
19.0
(12.1 to 24.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab + Capecitabine, Capecitabine
Comments Kaplan-Meier methodology estimated median PFS
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1315
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.691
Confidence Interval (2-Sided) 95%
0.429 to 1.114
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Icrucumab + Capecitabine, Capecitabine
Comments Kaplan-Meier methodology estimated median PFS
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0851
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.480
Confidence Interval (2-Sided) 95%
0.938 to 2.335
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival is defined as the time from the date of randomization to the date of death from any cause. If the participant is alive at the end of the follow-up period or is lost to follow-up, OS will be censored on the last date the participant is known to be alive.
Time Frame From Date of Randomization until Death Due to Any Cause (Up To 160 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug; censored participants: Ramucirumab + Capecitabine = 21; Icrucumab + Capecitabine = 17; Capecitabine = 22 Participants were analyzed as per the randomization.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine Capecitabine
Hide Arm/Group Description:
Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants received 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

After radiographic diseases progression while on Capecitabine, participants were crossed-over to either Ramucirumab or Icrucumab;

Participants crossed-over to Ramucirumab + Capecitabine had received 10 mg/kg Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants crossed-over to Icrucumab + Capecitabine received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 52 49 49
Median (95% Confidence Interval)
Unit of Measure: Weeks
67.4
(41.3 to 82.6)
62.1
(41.0 to 84.0)
71.6
(57.4 to 89.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab + Capecitabine, Capecitabine
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0283
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.833
Confidence Interval (2-Sided) 95%
1.060 to 3.169
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Icrucumab + Capecitabine, Capecitabine
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1550
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.468
Confidence Interval (2-Sided) 95%
0.862 to 2.501
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Objective Response Rate (ORR)
Hide Description 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 was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 mm. PR was 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 and the appearance of ≥1 new lesions was progression.
Time Frame From Date of Randomization until Disease Progression/Recurrence (Up to 97 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine Capecitabine
Hide Arm/Group Description:
Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants received 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

After radiographic diseases progression while on Capecitabine, participants were crossed-over to either Ramucirumab or Icrucumab;

Participants crossed-over to Ramucirumab + Capecitabine had received 10 mg/kg Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants crossed-over to Icrucumab + Capecitabine received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 52 49 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
28.8
(17.1 to 43.1)
20.4
(10.2 to 34.3)
34.7
(21.7 to 49.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab + Capecitabine, Capecitabine
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6691
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Icrucumab + Capecitabine, Capecitabine
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1743
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Duration of Response
Hide Description Duration of response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that the criteria for progressive disease (PD) is met (taking as a reference for PD that smallest measurement recorded since the treatment started), or death, is objectively documented.CR was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 mm. PR was 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.PD defined as ≥20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Sum must also have demonstrated an absolute increase of ≥5 mm, or the appearance of 1 or more new lesions was considered progression.
Time Frame From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 97 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had CR/PR.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine Capecitabine
Hide Arm/Group Description:
Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants received 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

After radiographic diseases progression while on Capecitabine, participants were crossed-over to either Ramucirumab or Icrucumab;

Participants crossed-over to Ramucirumab + Capecitabine had received 10 mg/kg Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants crossed-over to Icrucumab + Capecitabine received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 15 10 17
Median (95% Confidence Interval)
Unit of Measure: weeks
43.1
(12.0 to 49.0)
20.1
(1.9 to 33.9)
17.1
(6.4 to 30.7)
5.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description

Adverse event (AE) will be regarded as treatment-emergent if onset date occurs any time on or after the administration of the first dose of study treatment up to 30 days after the last dose of study treatment (or up to any time if related to study treatment); or it occurs prior to first dose date and worsens while on therapy or up to 30 days after the last dose of study treatment (or up to any time if related to study treatment).

A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time Frame Up To 160 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine Capecitabine
Hide Arm/Group Description:
Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants received 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

After radiographic diseases progression while on Capecitabine, participants were crossed-over to either Ramucirumab or Icrucumab;

Participants crossed-over to Ramucirumab + Capecitabine had received 10 mg/kg Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants crossed-over to Icrucumab + Capecitabine received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 52 49 49
Measure Type: Count of Participants
Unit of Measure: Participants
52 49 48
6.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAEs)
Hide Description

SAE was defined as any untoward medical occurrence that at any dose:

Resulted in death; Was life-threatening; Required inpatient hospitalization or caused prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect; Required intervention to prevent permanent impairment/damage; Was an important medical event (defined as a medical event that may not have been immediately life-threatening or resulted in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention to prevent one of the other serious outcomes listed in the definition above).

A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time Frame Up To 160 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine Capecitabine
Hide Arm/Group Description:
Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants received 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

After radiographic diseases progression while on Capecitabine, participants were crossed-over to either Ramucirumab or Icrucumab;

Participants crossed-over to Ramucirumab + Capecitabine had received 10 mg/kg Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.

Participants crossed-over to Icrucumab + Capecitabine received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 52 49 49
Measure Type: Count of Participants
Unit of Measure: Participants
20 25 6
7.Secondary Outcome
Title Maximum Concentration (Cmax) Ramucirumab Drug Product (DP) or Icrucumab
Hide Description [Not Specified]
Time Frame Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Hide Outcome Measure Data
Hide Analysis Population Description

For ramucirumab, all randomized participants who received at least one dose of study drug & had evaluable pharmacokinetic (PK) samples.

For icrucumab, zero participants analyzed as reliable PK parameters could not be estimated using non-compartmental PK analysis due to insufficient number of samples.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine
Hide Arm/Group Description:
Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 11 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Microgram per milliliter
308
(25%)
8.Secondary Outcome
Title Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab
Hide Description Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab.
Time Frame Cycle 2,4,6,8,0,12,14,16,18,22: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Hide Outcome Measure Data
Hide Analysis Population Description

For ramucirumab, all randomized participants who received at least one dose of study drug & had evaluable pharmacokinetic (PK) samples.

For icrucumab, zero participants analyzed as reliable PK parameters could not be estimated using non-compartmental PK analysis due to insufficient number of samples.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine
Hide Arm/Group Description:
Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 12 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Micro gram per milliliter
Cycle 2 Number Analyzed 12 participants 0 participants
23.7
(58%)
Cycle 4 Number Analyzed 4 participants 0 participants
80.6
(67%)
Cycle 6 Number Analyzed 4 participants 0 participants
44.7
(83%)
Cycle 8 Number Analyzed 3 participants 0 participants
65.8
(43%)
Cycle 10 Number Analyzed 4 participants 0 participants
66.8
(37%)
Cycle 12 Number Analyzed 3 participants 0 participants
74.3
(38%)
Cycle 14 Number Analyzed 1 participants 0 participants
62.5
Cycle 16 Number Analyzed 1 participants 0 participants
50.5
Cycle 18 Number Analyzed 1 participants 0 participants
50.5
Cycle 22 Number Analyzed 1 participants 0 participants
55.0
9.Secondary Outcome
Title Area Under the Concentration Versus Time Curve From Time Zero to Infinity of Ramucirumab or Icrucumab
Hide Description Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity of Ramucirumab and Icrucumab.
Time Frame Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Hide Outcome Measure Data
Hide Analysis Population Description

For ramucirumab, all randomized participants who received at least one dose of study drug & had evaluable pharmacokinetic (PK) samples.

For icrucumab, zero participants analyzed as reliable PK parameters could not be estimated using non-compartmental PK analysis due to insufficient number of samples.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine
Hide Arm/Group Description:
Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 7 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram*hour/mL
54400
(42%)
10.Secondary Outcome
Title Terminal Half-life (t½) of Ramucirumab or Icrucumab
Hide Description Terminal half-life (t½) of Ramucirumab and Icrucumab.
Time Frame Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Hide Outcome Measure Data
Hide Analysis Population Description

For ramucirumab, all randomized participants who received at least one dose of study drug & had evaluable pharmacokinetic (PK) samples.

For icrucumab, zero participants analyzed as reliable PK parameters could not be estimated using non-compartmental PK analysis due to insufficient number of samples.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine
Hide Arm/Group Description:
Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 7 0
Geometric Mean (Full Range)
Unit of Measure: Days
6.80
(5.22 to 8.57)
11.Secondary Outcome
Title Clearance (Cl) of Ramucirumab or Icrucumab
Hide Description Clearance (Cl) of Ramucirumab and Icrucumab.
Time Frame Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Hide Outcome Measure Data
Hide Analysis Population Description

For ramucirumab, all randomized participants who received at least one dose of study drug & had evaluable pharmacokinetic (PK) samples.

For icrucumab, zero participants analyzed as reliable PK parameters could not be estimated using non-compartmental PK analysis due to insufficient number of samples.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine
Hide Arm/Group Description:
Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 7 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters per hour
0.0141
(34%)
12.Secondary Outcome
Title Volume of Distribution at Steady State (Vss) of Ramucirumab or Icrucumab
Hide Description Volume of Distribution at Steady State (Vss) of Ramucirumab and Icrucumab.
Time Frame Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Hide Outcome Measure Data
Hide Analysis Population Description

For ramucirumab, all randomized participants who received at least one dose of study drug & had evaluable pharmacokinetic (PK) samples.

For icrucumab, zero participants analyzed as reliable PK parameters could not be estimated using non-compartmental PK analysis due to insufficient number of samples.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine
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Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 11 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters
3.17
(18%)
13.Secondary Outcome
Title Number of Participants With Anti-Ramucirumab and Anti-Icrucumab Antibodies
Hide Description [Not Specified]
Time Frame Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Hide Outcome Measure Data
Hide Analysis Population Description

For ramucirumab, Aall randomized participants who received at least one dose of study drug and had evaluable serum samples for antibody assessment.

For icrucumab, zero participants analyzed as antibody assessment data was not collected for Icrucumab.
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine
Hide Arm/Group Description:
Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per square meter (mg/m^2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 mg/m^2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
Overall Number of Participants Analyzed 43 0
Measure Type: Count of Participants
Unit of Measure: Participants
Treatment emergent antibody 0
Neutralizing antibody 0
Time Frame Up To 160 Weeks
Adverse Event Reporting Description All randomized participants who received at least one dose of study drug.
 
Arm/Group Title Ramucirumab + Capecitabine Icrucumab + Capecitabine Capecitabine Crossover to Ramucirumab DP + Capecitabine Crossover to Icrucumab + Capecitabine
Hide Arm/Group Description Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per meter square (mg/m*2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle. Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 milligram per meter square (mg/m*2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle. Participants received 1000 mg/m*2 of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle. Participants received 10 milligram per kilogram (mg/kg) Ramucirumab intravenously on day 1 of 21 days cycle along with 1000 milligram per meter square (mg/m*2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle. Participants received 12 mg/kg Icrucumab intravenously on day 1 and day 8 of 21 day cycle along with 1000 milligram per meter square (mg/m*2) of Capecitabine twice daily orally on days 1 to 14 of 21 days cycle.
All-Cause Mortality
Ramucirumab + Capecitabine Icrucumab + Capecitabine Capecitabine Crossover to Ramucirumab DP + Capecitabine Crossover to Icrucumab + Capecitabine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
Ramucirumab + Capecitabine Icrucumab + Capecitabine Capecitabine Crossover to Ramucirumab DP + Capecitabine Crossover to Icrucumab + Capecitabine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/52 (38.46%)      25/49 (51.02%)      6/49 (12.24%)      5/29 (17.24%)      0/1 (0.00%)    
Blood and lymphatic system disorders           
Anaemia † 1  0/52 (0.00%)  0 2/49 (4.08%)  2 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Pancytopenia † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Cardiac disorders           
Acute myocardial infarction † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Atrial fibrillation † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Cardiac failure † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Cardiogenic shock † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Palpitations † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Pericardial effusion † 1  0/52 (0.00%)  0 4/49 (8.16%)  4 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Right ventricular failure † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Gastrointestinal disorders           
Abdominal pain † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 1/49 (2.04%)  2 0/29 (0.00%)  0 0/1 (0.00%)  0
Ascites † 1  3/52 (5.77%)  3 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Colitis ulcerative † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Constipation † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Diarrhoea † 1  0/52 (0.00%)  0 2/49 (4.08%)  2 1/49 (2.04%)  2 0/29 (0.00%)  0 0/1 (0.00%)  0
Duodenal stenosis † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Haematemesis † 1  0/52 (0.00%)  0 0/49 (0.00%)  0 0/49 (0.00%)  0 1/29 (3.45%)  1 0/1 (0.00%)  0
Haemorrhoidal haemorrhage † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Melaena † 1  0/52 (0.00%)  0 0/49 (0.00%)  0 0/49 (0.00%)  0 1/29 (3.45%)  1 0/1 (0.00%)  0
Nausea † 1  0/52 (0.00%)  0 2/49 (4.08%)  2 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Stomatitis † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Vomiting † 1  0/52 (0.00%)  0 2/49 (4.08%)  2 2/49 (4.08%)  2 1/29 (3.45%)  1 0/1 (0.00%)  0
General disorders           
Asthenia † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Fatigue † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Mucosal inflammation † 1  2/52 (3.85%)  2 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Non-cardiac chest pain † 1  0/52 (0.00%)  0 1/49 (2.04%)  2 0/49 (0.00%)  0 1/29 (3.45%)  1 0/1 (0.00%)  0
Pain † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Pyrexia † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Hepatobiliary disorders           
Bile duct stenosis † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Hyperbilirubinaemia † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Jaundice † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Infections and infestations           
Cellulitis † 1  0/52 (0.00%)  0 0/49 (0.00%)  0 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Clostridium difficile infection † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Pneumonia † 1  0/52 (0.00%)  0 2/49 (4.08%)  3 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Injury, poisoning and procedural complications           
Medication error † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Road traffic accident † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Wound † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Investigations           
Ejection fraction decreased † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Metabolism and nutrition disorders           
Decreased appetite † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Dehydration † 1  2/52 (3.85%)  2 4/49 (8.16%)  4 0/49 (0.00%)  0 1/29 (3.45%)  1 0/1 (0.00%)  0
Failure to thrive † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Hypocalcaemia † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Hyponatraemia † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Back pain † 1  1/52 (1.92%)  1 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Bone pain † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Musculoskeletal chest pain † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Pain in extremity † 1  0/52 (0.00%)  0 0/49 (0.00%)  0 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Brain neoplasm malignant † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Haemangioma † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 1/29 (3.45%)  1 0/1 (0.00%)  0
Haemangioma of skin † 1  0/52 (0.00%)  0 0/49 (0.00%)  0 0/49 (0.00%)  0 1/29 (3.45%)  1 0/1 (0.00%)  0
Malignant neoplasm progression † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Malignant pleural effusion † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Neoplasm progression † 1  0/52 (0.00%)  0 0/49 (0.00%)  0 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Nervous system disorders           
Cerebrovascular accident † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Dizziness † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Presyncope † 1  0/52 (0.00%)  0 0/49 (0.00%)  0 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Syncope † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Psychiatric disorders           
Mental status changes † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Renal and urinary disorders           
Hydronephrosis † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Renal failure † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Renal failure acute † 1  0/52 (0.00%)  0 0/49 (0.00%)  0 0/49 (0.00%)  0 1/29 (3.45%)  1 0/1 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Acute respiratory failure † 1  0/52 (0.00%)  0 1/49 (2.04%)  2 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Atelectasis † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Dyspnoea † 1  4/52 (7.69%)  4 3/49 (6.12%)  4 0/49 (0.00%)  0 1/29 (3.45%)  1 0/1 (0.00%)  0
Pleural effusion † 1  2/52 (3.85%)  2 8/49 (16.33%)  9 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Pulmonary embolism † 1  0/52 (0.00%)  0 2/49 (4.08%)  2 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Pulmonary oedema † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Respiratory failure † 1  1/52 (1.92%)  1 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Skin and subcutaneous tissue disorders           
Palmar-plantar erythrodysaesthesia syndrome † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Vascular disorders           
Deep vein thrombosis † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Hypertension † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Hypotension † 1  1/52 (1.92%)  1 1/49 (2.04%)  1 0/49 (0.00%)  0 1/29 (3.45%)  1 0/1 (0.00%)  0
Lymphoedema † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ramucirumab + Capecitabine Icrucumab + Capecitabine Capecitabine Crossover to Ramucirumab DP + Capecitabine Crossover to Icrucumab + Capecitabine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   51/52 (98.08%)      49/49 (100.00%)      48/49 (97.96%)      29/29 (100.00%)      1/1 (100.00%)    
Blood and lymphatic system disorders           
Anaemia † 1  7/52 (13.46%)  8 14/49 (28.57%)  35 12/49 (24.49%)  28 3/29 (10.34%)  5 1/1 (100.00%)  1
Leukopenia † 1  4/52 (7.69%)  5 0/49 (0.00%)  0 7/49 (14.29%)  13 1/29 (3.45%)  1 0/1 (0.00%)  0
Lymphopenia † 1  5/52 (9.62%)  16 1/49 (2.04%)  15 3/49 (6.12%)  15 3/29 (10.34%)  3 0/1 (0.00%)  0
Neutropenia † 1  8/52 (15.38%)  16 6/49 (12.24%)  10 6/49 (12.24%)  10 2/29 (6.90%)  2 0/1 (0.00%)  0
Thrombocytopenia † 1  9/52 (17.31%)  13 1/49 (2.04%)  2 9/49 (18.37%)  10 5/29 (17.24%)  11 0/1 (0.00%)  0
Cardiac disorders           
Pericardial effusion † 1  0/52 (0.00%)  0 4/49 (8.16%)  4 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Tachycardia † 1  1/52 (1.92%)  1 5/49 (10.20%)  6 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Endocrine disorders           
Hypothyroidism † 1  0/52 (0.00%)  0 0/49 (0.00%)  0 0/49 (0.00%)  0 2/29 (6.90%)  2 0/1 (0.00%)  0
Eye disorders           
Conjunctivitis † 1  4/52 (7.69%)  6 0/49 (0.00%)  0 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Dry eye † 1  3/52 (5.77%)  4 3/49 (6.12%)  3 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Lacrimation increased † 1  4/52 (7.69%)  4 6/49 (12.24%)  6 2/49 (4.08%)  2 1/29 (3.45%)  2 0/1 (0.00%)  0
Periorbital oedema † 1  2/52 (3.85%)  2 6/49 (12.24%)  7 0/49 (0.00%)  0 1/29 (3.45%)  1 0/1 (0.00%)  0
Vision blurred † 1  2/52 (3.85%)  2 1/49 (2.04%)  1 0/49 (0.00%)  0 3/29 (10.34%)  3 1/1 (100.00%)  1
Gastrointestinal disorders           
Abdominal distension † 1  2/52 (3.85%)  2 3/49 (6.12%)  4 3/49 (6.12%)  3 3/29 (10.34%)  3 0/1 (0.00%)  0
Abdominal pain † 1  9/52 (17.31%)  11 6/49 (12.24%)  10 4/49 (8.16%)  6 2/29 (6.90%)  2 0/1 (0.00%)  0
Abdominal pain lower † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 3/49 (6.12%)  3 1/29 (3.45%)  2 0/1 (0.00%)  0
Abdominal pain upper † 1  3/52 (5.77%)  4 3/49 (6.12%)  3 3/49 (6.12%)  3 3/29 (10.34%)  3 1/1 (100.00%)  1
Constipation † 1  18/52 (34.62%)  25 14/49 (28.57%)  16 17/49 (34.69%)  25 7/29 (24.14%)  8 0/1 (0.00%)  0
Diarrhoea † 1  22/52 (42.31%)  47 20/49 (40.82%)  38 27/49 (55.10%)  58 5/29 (17.24%)  6 0/1 (0.00%)  0
Dyspepsia † 1  6/52 (11.54%)  7 5/49 (10.20%)  6 3/49 (6.12%)  3 2/29 (6.90%)  2 0/1 (0.00%)  0
Gastrooesophageal reflux disease † 1  2/52 (3.85%)  2 5/49 (10.20%)  5 3/49 (6.12%)  3 1/29 (3.45%)  1 0/1 (0.00%)  0
Gingival bleeding † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 2/29 (6.90%)  4 0/1 (0.00%)  0
Nausea † 1  27/52 (51.92%)  47 37/49 (75.51%)  53 26/49 (53.06%)  39 8/29 (27.59%)  16 0/1 (0.00%)  0
Oral pain † 1  2/52 (3.85%)  2 0/49 (0.00%)  0 3/49 (6.12%)  4 0/29 (0.00%)  0 0/1 (0.00%)  0
Stomatitis † 1  14/52 (26.92%)  20 4/49 (8.16%)  7 7/49 (14.29%)  12 5/29 (17.24%)  6 0/1 (0.00%)  0
Toothache † 1  3/52 (5.77%)  3 0/49 (0.00%)  0 1/49 (2.04%)  1 1/29 (3.45%)  1 0/1 (0.00%)  0
Vomiting † 1  19/52 (36.54%)  23 25/49 (51.02%)  31 14/49 (28.57%)  25 7/29 (24.14%)  10 0/1 (0.00%)  0
General disorders           
Asthenia † 1  6/52 (11.54%)  7 4/49 (8.16%)  5 1/49 (2.04%)  1 1/29 (3.45%)  1 0/1 (0.00%)  0
Chills † 1  4/52 (7.69%)  4 2/49 (4.08%)  2 2/49 (4.08%)  2 3/29 (10.34%)  3 1/1 (100.00%)  1
Face oedema † 1  1/52 (1.92%)  1 9/49 (18.37%)  12 0/49 (0.00%)  0 0/29 (0.00%)  0 1/1 (100.00%)  1
Fatigue † 1  27/52 (51.92%)  54 27/49 (55.10%)  43 26/49 (53.06%)  36 11/29 (37.93%)  15 0/1 (0.00%)  0
Influenza like illness † 1  6/52 (11.54%)  7 2/49 (4.08%)  2 1/49 (2.04%)  1 1/29 (3.45%)  1 0/1 (0.00%)  0
Mucosal inflammation † 1  8/52 (15.38%)  14 4/49 (8.16%)  6 9/49 (18.37%)  16 1/29 (3.45%)  1 0/1 (0.00%)  0
Non-cardiac chest pain † 1  1/52 (1.92%)  1 2/49 (4.08%)  4 1/49 (2.04%)  1 0/29 (0.00%)  0 1/1 (100.00%)  1
Oedema † 1  1/52 (1.92%)  1 3/49 (6.12%)  4 1/49 (2.04%)  2 1/29 (3.45%)  1 0/1 (0.00%)  0
Oedema peripheral † 1  13/52 (25.00%)  21 19/49 (38.78%)  37 6/49 (12.24%)  7 5/29 (17.24%)  8 1/1 (100.00%)  1
Pain † 1  5/52 (9.62%)  8 2/49 (4.08%)  2 3/49 (6.12%)  3 1/29 (3.45%)  1 0/1 (0.00%)  0
Pyrexia † 1  14/52 (26.92%)  18 7/49 (14.29%)  8 4/49 (8.16%)  6 5/29 (17.24%)  6 0/1 (0.00%)  0
Hepatobiliary disorders           
Hyperbilirubinaemia † 1  1/52 (1.92%)  1 0/49 (0.00%)  0 0/49 (0.00%)  0 2/29 (6.90%)  4 0/1 (0.00%)  0
Infections and infestations           
Nasopharyngitis † 1  5/52 (9.62%)  5 3/49 (6.12%)  3 2/49 (4.08%)  3 2/29 (6.90%)  2 0/1 (0.00%)  0
Sinusitis † 1  7/52 (13.46%)  13 0/49 (0.00%)  0 3/49 (6.12%)  3 2/29 (6.90%)  2 0/1 (0.00%)  0
Upper respiratory tract infection † 1  3/52 (5.77%)  3 1/49 (2.04%)  1 2/49 (4.08%)  2 3/29 (10.34%)  3 0/1 (0.00%)  0
Urinary tract infection † 1  4/52 (7.69%)  8 3/49 (6.12%)  3 4/49 (8.16%)  6 1/29 (3.45%)  1 0/1 (0.00%)  0
Injury, poisoning and procedural complications           
Contusion † 1  4/52 (7.69%)  7 1/49 (2.04%)  1 0/49 (0.00%)  0 2/29 (6.90%)  3 0/1 (0.00%)  0
Infusion related reaction † 1  2/52 (3.85%)  3 4/49 (8.16%)  6 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Investigations           
Activated partial thromboplastin time prolonged † 1  1/52 (1.92%)  1 2/49 (4.08%)  2 1/49 (2.04%)  1 2/29 (6.90%)  3 0/1 (0.00%)  0
Alanine aminotransferase increased † 1  5/52 (9.62%)  12 1/49 (2.04%)  1 5/49 (10.20%)  6 3/29 (10.34%)  6 0/1 (0.00%)  0
Aspartate aminotransferase increased † 1  9/52 (17.31%)  14 2/49 (4.08%)  3 7/49 (14.29%)  7 2/29 (6.90%)  6 0/1 (0.00%)  0
Blood alkaline phosphatase increased † 1  4/52 (7.69%)  9 2/49 (4.08%)  2 4/49 (8.16%)  4 1/29 (3.45%)  1 0/1 (0.00%)  0
Blood bilirubin increased † 1  3/52 (5.77%)  3 1/49 (2.04%)  1 1/49 (2.04%)  1 2/29 (6.90%)  3 0/1 (0.00%)  0
Blood creatinine increased † 1  4/52 (7.69%)  4 2/49 (4.08%)  12 1/49 (2.04%)  2 1/29 (3.45%)  1 0/1 (0.00%)  0
Blood lactate dehydrogenase increased † 1  3/52 (5.77%)  6 2/49 (4.08%)  2 1/49 (2.04%)  2 2/29 (6.90%)  2 0/1 (0.00%)  0
International normalised ratio increased † 1  0/52 (0.00%)  0 0/49 (0.00%)  0 1/49 (2.04%)  1 2/29 (6.90%)  3 0/1 (0.00%)  0
Neutrophil count decreased † 1  4/52 (7.69%)  9 2/49 (4.08%)  3 2/49 (4.08%)  5 1/29 (3.45%)  2 1/1 (100.00%)  1
Platelet count decreased † 1  3/52 (5.77%)  4 0/49 (0.00%)  0 1/49 (2.04%)  1 2/29 (6.90%)  3 0/1 (0.00%)  0
Weight decreased † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 4/49 (8.16%)  4 1/29 (3.45%)  2 0/1 (0.00%)  0
Weight increased † 1  2/52 (3.85%)  2 3/49 (6.12%)  3 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
White blood cell count decreased † 1  2/52 (3.85%)  3 2/49 (4.08%)  2 4/49 (8.16%)  4 2/29 (6.90%)  2 0/1 (0.00%)  0
Metabolism and nutrition disorders           
Decreased appetite † 1  17/52 (32.69%)  26 11/49 (22.45%)  16 10/49 (20.41%)  17 6/29 (20.69%)  9 1/1 (100.00%)  1
Dehydration † 1  4/52 (7.69%)  4 7/49 (14.29%)  7 3/49 (6.12%)  4 1/29 (3.45%)  1 0/1 (0.00%)  0
Hyperglycaemia † 1  9/52 (17.31%)  15 4/49 (8.16%)  7 2/49 (4.08%)  2 3/29 (10.34%)  4 0/1 (0.00%)  0
Hypoalbuminaemia † 1  4/52 (7.69%)  8 3/49 (6.12%)  7 1/49 (2.04%)  1 3/29 (10.34%)  4 0/1 (0.00%)  0
Hypocalcaemia † 1  5/52 (9.62%)  7 4/49 (8.16%)  22 6/49 (12.24%)  9 4/29 (13.79%)  5 0/1 (0.00%)  0
Hypokalaemia † 1  12/52 (23.08%)  18 7/49 (14.29%)  10 12/49 (24.49%)  17 3/29 (10.34%)  3 0/1 (0.00%)  0
Hyponatraemia † 1  3/52 (5.77%)  5 3/49 (6.12%)  4 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Hypophosphataemia † 1  1/52 (1.92%)  1 2/49 (4.08%)  4 0/49 (0.00%)  0 3/29 (10.34%)  5 0/1 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Arthralgia † 1  11/52 (21.15%)  19 2/49 (4.08%)  2 8/49 (16.33%)  13 3/29 (10.34%)  4 1/1 (100.00%)  2
Back pain † 1  10/52 (19.23%)  15 6/49 (12.24%)  8 8/49 (16.33%)  9 6/29 (20.69%)  9 0/1 (0.00%)  0
Muscle spasms † 1  6/52 (11.54%)  8 0/49 (0.00%)  0 5/49 (10.20%)  5 2/29 (6.90%)  3 0/1 (0.00%)  0
Muscular weakness † 1  2/52 (3.85%)  3 1/49 (2.04%)  1 0/49 (0.00%)  0 1/29 (3.45%)  1 1/1 (100.00%)  3
Musculoskeletal chest pain † 1  7/52 (13.46%)  7 3/49 (6.12%)  3 6/49 (12.24%)  8 2/29 (6.90%)  2 0/1 (0.00%)  0
Musculoskeletal pain † 1  6/52 (11.54%)  7 1/49 (2.04%)  1 3/49 (6.12%)  4 1/29 (3.45%)  1 0/1 (0.00%)  0
Myalgia † 1  9/52 (17.31%)  10 4/49 (8.16%)  5 3/49 (6.12%)  3 2/29 (6.90%)  3 1/1 (100.00%)  1
Neck pain † 1  6/52 (11.54%)  9 3/49 (6.12%)  3 0/49 (0.00%)  0 1/29 (3.45%)  3 0/1 (0.00%)  0
Pain in extremity † 1  15/52 (28.85%)  29 3/49 (6.12%)  3 6/49 (12.24%)  7 3/29 (10.34%)  6 0/1 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Haemangioma † 1  0/52 (0.00%)  0 0/49 (0.00%)  0 0/49 (0.00%)  0 2/29 (6.90%)  3 0/1 (0.00%)  0
Metastases to central nervous system † 1  0/52 (0.00%)  0 3/49 (6.12%)  3 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Nervous system disorders           
Dizziness † 1  6/52 (11.54%)  8 6/49 (12.24%)  7 3/49 (6.12%)  3 3/29 (10.34%)  4 0/1 (0.00%)  0
Dysgeusia † 1  6/52 (11.54%)  8 6/49 (12.24%)  6 3/49 (6.12%)  3 3/29 (10.34%)  4 0/1 (0.00%)  0
Headache † 1  26/52 (50.00%)  60 9/49 (18.37%)  11 11/49 (22.45%)  18 13/29 (44.83%)  16 1/1 (100.00%)  1
Migraine † 1  1/52 (1.92%)  2 0/49 (0.00%)  0 0/49 (0.00%)  0 2/29 (6.90%)  4 0/1 (0.00%)  0
Neuropathy peripheral † 1  10/52 (19.23%)  17 6/49 (12.24%)  8 4/49 (8.16%)  5 2/29 (6.90%)  3 0/1 (0.00%)  0
Paraesthesia † 1  4/52 (7.69%)  4 3/49 (6.12%)  3 2/49 (4.08%)  2 1/29 (3.45%)  1 0/1 (0.00%)  0
Peripheral sensory neuropathy † 1  6/52 (11.54%)  6 5/49 (10.20%)  10 2/49 (4.08%)  2 0/29 (0.00%)  0 0/1 (0.00%)  0
Psychiatric disorders           
Anxiety † 1  6/52 (11.54%)  6 7/49 (14.29%)  8 5/49 (10.20%)  6 1/29 (3.45%)  1 0/1 (0.00%)  0
Depression † 1  6/52 (11.54%)  6 6/49 (12.24%)  6 4/49 (8.16%)  6 1/29 (3.45%)  1 0/1 (0.00%)  0
Insomnia † 1  7/52 (13.46%)  7 9/49 (18.37%)  9 12/49 (24.49%)  14 3/29 (10.34%)  3 0/1 (0.00%)  0
Renal and urinary disorders           
Dysuria † 1  0/52 (0.00%)  0 0/49 (0.00%)  0 3/49 (6.12%)  3 0/29 (0.00%)  0 0/1 (0.00%)  0
Proteinuria † 1  5/52 (9.62%)  7 3/49 (6.12%)  3 0/49 (0.00%)  0 3/29 (10.34%)  3 0/1 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Cough † 1  21/52 (40.38%)  27 10/49 (20.41%)  11 9/49 (18.37%)  10 2/29 (6.90%)  2 0/1 (0.00%)  0
Dysphonia † 1  0/52 (0.00%)  0 5/49 (10.20%)  5 1/49 (2.04%)  1 2/29 (6.90%)  2 0/1 (0.00%)  0
Dyspnoea † 1  19/52 (36.54%)  29 16/49 (32.65%)  19 9/49 (18.37%)  10 7/29 (24.14%)  11 0/1 (0.00%)  0
Dyspnoea exertional † 1  2/52 (3.85%)  2 1/49 (2.04%)  1 2/49 (4.08%)  2 3/29 (10.34%)  3 0/1 (0.00%)  0
Epistaxis † 1  9/52 (17.31%)  12 0/49 (0.00%)  0 3/49 (6.12%)  3 5/29 (17.24%)  7 0/1 (0.00%)  0
Nasal congestion † 1  5/52 (9.62%)  6 0/49 (0.00%)  0 2/49 (4.08%)  2 2/29 (6.90%)  5 0/1 (0.00%)  0
Oropharyngeal pain † 1  5/52 (9.62%)  6 3/49 (6.12%)  3 5/49 (10.20%)  5 2/29 (6.90%)  2 0/1 (0.00%)  0
Paranasal sinus hypersecretion † 1  5/52 (9.62%)  5 0/49 (0.00%)  0 1/49 (2.04%)  1 2/29 (6.90%)  2 0/1 (0.00%)  0
Pleural effusion † 1  3/52 (5.77%)  4 9/49 (18.37%)  10 0/49 (0.00%)  0 1/29 (3.45%)  1 0/1 (0.00%)  0
Productive cough † 1  3/52 (5.77%)  3 2/49 (4.08%)  2 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Rhinorrhoea † 1  6/52 (11.54%)  6 2/49 (4.08%)  2 1/49 (2.04%)  1 1/29 (3.45%)  1 0/1 (0.00%)  0
Sinus congestion † 1  2/52 (3.85%)  2 1/49 (2.04%)  1 1/49 (2.04%)  1 3/29 (10.34%)  3 0/1 (0.00%)  0
Skin and subcutaneous tissue disorders           
Dry skin † 1  3/52 (5.77%)  3 0/49 (0.00%)  0 5/49 (10.20%)  6 1/29 (3.45%)  1 0/1 (0.00%)  0
Erythema † 1  3/52 (5.77%)  3 3/49 (6.12%)  3 7/49 (14.29%)  9 0/29 (0.00%)  0 0/1 (0.00%)  0
Palmar-plantar erythrodysaesthesia syndrome † 1  37/52 (71.15%)  127 15/49 (30.61%)  38 35/49 (71.43%)  114 17/29 (58.62%)  40 0/1 (0.00%)  0
Pruritus † 1  2/52 (3.85%)  5 2/49 (4.08%)  2 3/49 (6.12%)  3 3/29 (10.34%)  5 0/1 (0.00%)  0
Rash † 1  4/52 (7.69%)  4 1/49 (2.04%)  1 3/49 (6.12%)  3 2/29 (6.90%)  2 0/1 (0.00%)  0
Rash macular † 1  3/52 (5.77%)  13 2/49 (4.08%)  2 0/49 (0.00%)  0 0/29 (0.00%)  0 0/1 (0.00%)  0
Skin hyperpigmentation † 1  7/52 (13.46%)  8 2/49 (4.08%)  2 4/49 (8.16%)  4 2/29 (6.90%)  2 0/1 (0.00%)  0
Vascular disorders           
Flushing † 1  2/52 (3.85%)  2 3/49 (6.12%)  4 1/49 (2.04%)  1 1/29 (3.45%)  1 0/1 (0.00%)  0
Hot flush † 1  1/52 (1.92%)  2 0/49 (0.00%)  0 4/49 (8.16%)  8 1/29 (3.45%)  2 0/1 (0.00%)  0
Hypertension † 1  16/52 (30.77%)  35 1/49 (2.04%)  1 1/49 (2.04%)  1 7/29 (24.14%)  8 0/1 (0.00%)  0
Hypotension † 1  1/52 (1.92%)  1 5/49 (10.20%)  5 1/49 (2.04%)  1 0/29 (0.00%)  0 0/1 (0.00%)  0
Lymphoedema † 1  0/52 (0.00%)  0 1/49 (2.04%)  1 4/49 (8.16%)  4 2/29 (6.90%)  2 0/1 (0.00%)  0
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The disclosure restriction on PI is for five years after the study conclusion/termination, after five years disclosure restriction on PI is that sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
EMail: ClinicalTrials.gov@lilly.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01234402    
Other Study ID Numbers: 13944
CP20-0903 ( Other Identifier: ImClone LLC )
I4Y-IE-JCDD ( Other Identifier: Eli Lilly and Company )
First Submitted: November 3, 2010
First Posted: November 4, 2010
Results First Submitted: June 13, 2019
Results First Posted: August 14, 2019
Last Update Posted: August 14, 2019