A Study of Ramucirumab or Icrucumab in Colorectal Cancer
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01111604
Collaborator
(none)
158
17
3
40
9.3
0.2
Study Details
Study Description
Brief Summary
The purpose of this study is to determine if participants with metastatic colorectal cancer live longer without their cancer progressing when treated with standard chemotherapy, standard chemotherapy plus ramucirumab, or standard chemotherapy plus icrucumab.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The purpose of this study is to evaluate the progression-free survival (PFS) in participants with metastatic colorectal cancer when treated with 1 of 3 modified FOLFOX-6 (folinic acid [FA] + fluorouracil [5-FU] + oxaliplatin [mFOLFOX-6])-based regimens, as second-line therapy.
During 2010, there has been an identified shortage of injectable folinic acid (FA) in the United States. Levo-folinic acid (LFA) will be allowed as a substitute for FA in the mFOLFOX-6 chemotherapy regimen in circumstances in which FA is not available, to facilitate continuity of participant care.
Study Design
Study Type:
Interventional
Actual Enrollment
:
158 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of 5 FU/FA and Oxaliplatin (Modified FOLFOX 6) in Combination With Ramucirumab or IMC-18F1 or Without Investigational Therapy as Second Line Therapy in Patients With Metastatic Colorectal Cancer Following Disease Progression on First Line Irinotecan-based Therapy
Study Start Date
:
Aug 1, 2010
Actual Primary Completion Date
:
Dec 1, 2013
Actual Study Completion Date
:
Dec 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: mFOLFOX-6 mFOLFOX-6 |
Drug: mFOLFOX-6
Oxaliplatin: 85 milligram per square meter (mg/m²) IV every 2 weeks (Q2W)
FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable).
5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W
|
| Experimental: mFOLFOX-6 + Ramucirumab mFOLFOX-6 + Ramucirumab |
Biological: Ramucirumab
8 mg/kg IV Q2W
Other Names:
Drug: mFOLFOX-6
Oxaliplatin: 85 milligram per square meter (mg/m²) IV every 2 weeks (Q2W)
FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable).
5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W
|
| Experimental: mFOLFOX-6 + Icrucumab mFOLFOX-6 + Icrucumab |
Biological: Icrucumab
15 mg/kg IV Q2W
Other Names:
Drug: mFOLFOX-6
Oxaliplatin: 85 milligram per square meter (mg/m²) IV every 2 weeks (Q2W)
FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable).
5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival (PFS) [Baseline until Disease Progression or Death from Any Cause (Up to 95 Weeks)]
PFS is defined as the time from baseline until the date of disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1), or death from any cause, whichever was first. Participants who die without a reported prior progression will be considered to have progressed on the day of their death. Participants who did not progress, are lost to follow-up, or have missed two or more scheduled tumor assessments will be censored at the day of their last radiographic tumor assessment, if there are no post-baseline tumor measurements for a randomized and treated participant, the participant will be censored at the date of randomization. If death or progressive disease (PD) occurs after 2 or more missing radiographic visits, censoring will occur at the date of the last radiographic visit prior to the last visit.
Secondary Outcome Measures
- Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) [Baseline until Disease Progression (Up to 95 Weeks)]
The ORR is the percentage of participants with Complete Response (CR, the disappearance of target lesions and any pathological lymph nodes [target or non-target] taking as reference the baseline sum of diameters in response to treatment) or Partial Response (PR, at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters in response to treatment) according to RECIST v1.1 from the start of the treatment until disease progression.
- Overall Survival (OS) [Baseline Until Death from Any Cause (Up to 163 Weeks)]
Overall survival is defined as the time from baseline 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.
- Duration of Response (DoR) [Criteria First Met for CR or PR until Disease Progression or Death from Any Cause (Up to 95 Weeks)]
DoR was measured from the time measurement criteria are first met for Complete Response or Partial Response or until the first date that the criteria for disease progression or death from any cause. whichever is first recorded. As defined according to RECIST v1.1, CR is the disappearance of all non-nodal target lesions, and PR is the short axes of any target lymph nodes reduced to < 10 mm and at least a 30% decrease in the sum of the diameters of target lesions including the short axes of any target lymph nodes.)
- Pharmacokinetics (PK): Maximum Concentration (Cmax) at Cycle 5 [Cycle 5, 1 Hour Post End of Infusion]
Maximum concentration (1 hour post end of infusion, Cmax) is the concentration measured in serum.
- Pharmacokinetics (PK): Trough Serum Concentrations (Ctrough) at Cycle 5 [Cycle 5, Prior to Infusion]
Trough (prior to infusion, Ctrough) concentrations measured in serum.
- Maximum Concentration (Cmax) at Day 8 [Day 8 (cycles 1 and 5)]
Maximum concentration (Cmax) is the maximum peak concentration measured in blood plasma after drug infusion.
- Maximum Concentration (Cmax) at Day 15 [Day 15 (Cycles 1 and 5)]
Cmax is the maximum peak concentration measured in blood plasma after drug infusion.
- Minimum Concentration (Cmin) at Day 1 [Day 1 (cycles 1, 5, 9, and 13)]
Cmin is the minimum peak concentration measured in blood plasma after drug infusion.
- Minimum Concentration (Cmin) at Day 4 [Day 4 (cycles 1 and 5)]
Cmin is the minimum peak concentration measured in blood plasma after drug infusion.
- Minimum Concentration (Cmin) at Day 8 [Day 8 (cycles 1 and 5)]
Minimum concentration (Cmin) is the minimum peak concentration measured in blood plasma after drug infusion.
- Minimum Concentration (Cmin) at Day 15 [Day 15 (cycles 1 and 5)]
Minimum concentration (Cmin) is the minimum peak concentration measured in blood plasma after drug infusion.
- Number of Participants With Serum Ramucirumab Antibody Assessment [31 Weeks]
A sample will be considered positive for anti-Ramucirumab antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-Ramucirumab antibody level seen in healthy untreated individuals.
- Serum Anti-Icrucumab Antibody Assessment [31 Weeks]
A sample will be considered positive for anti-icrucumab antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-icrucumab antibody level seen in healthy untreated individuals.
- Number of Participants With Adverse Events [Baseline up to 165 weeks]
A summary of serious AEs (SAEs) and all other non-serious AEs regardless of causality, is located in the Reported Adverse Events module.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Disease progression on an irinotecan-based first-line chemotherapy regimen (ie FOLFIRI or CAPIRI [capecitabine + irinotecan], with or without bevacizumab)
-
Age ≥ 18 years
-
Life expectancy of ≥ 6 months
-
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 at study entry
-
Agrees to adequate contraception during the study period and for 12 weeks after the last dose of study medication
-
Provided signed informed consent
Exclusion Criteria:
-
Has received prior oxaliplatin-based chemotherapy for locally advanced unresectable or metastatic Colorectal Cancer (CRC) (Prior oxaliplatin-based adjuvant chemotherapy is allowed if the last dose of oxaliplatin was administered > 12 months prior to randomization)
-
Has documented and/or symptomatic brain or leptomeningeal metastases
-
Has an ongoing or active infection, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders
-
On chronic non-topical corticosteroid treatment. A participant discontinuing such treatment > 3 months prior to randomization is eligible
-
Has uncontrolled or poorly controlled hypertension on a standard regimen of antihypertensive therapy
-
Has a concurrent active malignancy. A participant with previous history of malignancy is eligible, provided that he/she has been disease free for > 3 years
-
If female, is pregnant (confirmed by serum beta human chorionic gonadotropin [βHCG] test) or lactating
-
Has received a prior autologous or allogeneic organ or tissue transplantation
-
Has undergone major surgery within 28 days prior to randomization
-
Has had a serious nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization
-
Has an elective or planned major surgery to be performed during the course of the trial
-
Has a history of inflammatory bowel disease requiring pharmacological and/or surgical intervention in the 12 months prior to randomization
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ImClone Investigational Site | Cincinnati | Ohio | United States | 45242 |
| 2 | ImClone Investigational Site | Columbia | South Carolina | United States | 29210 |
| 3 | ImClone Investigational Site | Nashville | Tennessee | United States | 37232 |
| 4 | ImClone Investigational Site | Calgary | Alberta | Canada | T2N 4N2 |
| 5 | ImClone Investigational Site | Edmonton | Alberta | Canada | T6G 1Z2 |
| 6 | ImClone Investigational Site | Kelowna | British Columbia | Canada | V1Y 5L3 |
| 7 | ImClone Investigational Site | Surrey | British Columbia | Canada | V3V 1Z2 |
| 8 | ImClone Investigational Site | Vancouver | British Columbia | Canada | V5Z 4E6 |
| 9 | ImClone Investigational Site | Halifax | Nova Scotia | Canada | B3H 1V7 |
| 10 | ImClone Investigational Site | Hamilton | Ontario | Canada | L8V 5C2 |
| 11 | ImClone Investigational Site | London | Ontario | Canada | N6A 4L6 |
| 12 | ImClone Investigational Site | Mississauga | Ontario | Canada | L5M 2N1 |
| 13 | ImClone Investigational Site | Oshawa | Ontario | Canada | L1G 2B9 |
| 14 | ImClone Investigational Site | Ottawa | Ontario | Canada | K1H 8L6 |
| 15 | ImClone Investigational Site | Toronto | Ontario | Canada | M5G 2M9 |
| 16 | ImClone Investigational Site | Windsor | Ontario | Canada | N8W 2X3 |
| 17 | ImClone Investigational Site | Montreal | Quebec | Canada | H2W 156 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01111604
Other Study ID Numbers:
- 13942
- CP20-0801
- I4Y-IE-JCDB
First Posted:
Apr 27, 2010
Last Update Posted:
Aug 6, 2019
Last Verified:
Jul 1, 2019
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Completers were defined as participants who had failure event (progressive disease, death), or were off treatment and censored due to study completion. |
| Arm/Group Title | mFOLFOX-6 | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|---|
| Arm/Group Description | mFOLFOX-6: Oxaliplatin: 85 milligram/meter squared, intravenous (mg/m², IV) infusion every 2 weeks (Q2W) Folinic acid (FA): 400 mg/m² IV infusion Q2W (or Levo-folinic acid [LFA]: 200 mg/m² Q2 weeks if FA is unavailable). Fluorouracil (5FU): 400 mg/m² bolus + 2400 mg/m² IV infusion Q2W | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W FA: 400 mg/m² IV infusion Q2 weeks (or LFA: 200 mg/m² Q2 weeks if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV infusion Q2W | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m2 Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W |
| Period Title: Overall Study | |||
| STARTED | 54 | 52 | 52 |
| Received at Least One Dose of Study Drug | 49 | 52 | 52 |
| COMPLETED | 46 | 52 | 49 |
| NOT COMPLETED | 8 | 0 | 3 |
Baseline Characteristics
| Arm/Group Title | mFOLFOX-6 | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab | Total |
|---|---|---|---|---|
| Arm/Group Description | mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m2 Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | Total of all reporting groups |
| Overall Participants | 49 | 52 | 52 | 153 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
60.8
(9.23)
|
59.9
(10.95)
|
58.2
(10.15)
|
59.6
(10.14)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
21
42.9%
|
21
40.4%
|
29
55.8%
|
71
46.4%
|
| Male |
28
57.1%
|
31
59.6%
|
23
44.2%
|
82
53.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
1.9%
|
1
0.7%
|
| Not Hispanic or Latino |
49
100%
|
52
100%
|
51
98.1%
|
152
99.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
7
14.3%
|
5
9.6%
|
7
13.5%
|
19
12.4%
|
| Native Hawaiian or Other Pacific Islander |
1
2%
|
0
0%
|
0
0%
|
1
0.7%
|
| Black or African American |
3
6.1%
|
1
1.9%
|
0
0%
|
4
2.6%
|
| White |
35
71.4%
|
45
86.5%
|
45
86.5%
|
125
81.7%
|
| More than one race |
0
0%
|
1
1.9%
|
0
0%
|
1
0.7%
|
| Unknown or Not Reported |
3
6.1%
|
0
0%
|
0
0%
|
3
2%
|
Outcome Measures
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | PFS is defined as the time from baseline until the date of disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1), or death from any cause, whichever was first. Participants who die without a reported prior progression will be considered to have progressed on the day of their death. Participants who did not progress, are lost to follow-up, or have missed two or more scheduled tumor assessments will be censored at the day of their last radiographic tumor assessment, if there are no post-baseline tumor measurements for a randomized and treated participant, the participant will be censored at the date of randomization. If death or progressive disease (PD) occurs after 2 or more missing radiographic visits, censoring will occur at the date of the last radiographic visit prior to the last visit. |
| Time Frame | Baseline until Disease Progression or Death from Any Cause (Up to 95 Weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent-to-Treatment (mITT) population includes all the randomized participants who received at least one dose study drug. In mFOLFOX-6, mFOLFOX-6+Ramucirumab and mFOLFOX-6 + Icrucumab, there were 13, 9 and 11 censored participants, respectively. |
| Arm/Group Title | mFOLFOX-6 | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|---|
| Arm/Group Description | mFOLFOX-6: Oxaliplatin: 85 per meter squared (mg/m²) IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV infusion Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV infusion Q2W FA: 400 mg/m² IV infusion Q2 weeks (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W |
| Measure Participants | 49 | 52 | 52 |
| Median (95% Confidence Interval) [Weeks] |
18.4
|
21.4
|
15.9
|
| Title | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) |
|---|---|
| Description | The ORR is the percentage of participants with Complete Response (CR, the disappearance of target lesions and any pathological lymph nodes [target or non-target] taking as reference the baseline sum of diameters in response to treatment) or Partial Response (PR, at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters in response to treatment) according to RECIST v1.1 from the start of the treatment until disease progression. |
| Time Frame | Baseline until Disease Progression (Up to 95 Weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population includes all the randomized participants who received at least one dose of study drug. |
| Arm/Group Title | mFOLFOX-6 | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|---|
| Arm/Group Description | mFOLFOX-6 mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² I.V. infusion q2 weeks (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² I.V. infusion q2 weeks (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² I.V. infusion Q2W |
| Measure Participants | 49 | 52 | 52 |
| Number (95% Confidence Interval) [percentage of participants] |
14
28.6%
|
3.8
7.3%
|
3.8
7.3%
|
| Title | Overall Survival (OS) |
|---|---|
| Description | Overall survival is defined as the time from baseline 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 | Baseline Until Death from Any Cause (Up to 163 Weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population includes all the randomized participants who received at least one dose of study drug. In mFOLFOX-6, mFOLFOX-6 + Ramucirumab, and mFOLFOX-6 + Icrucumab there were 12, 11, and 12 censored participants, respectively. |
| Arm/Group Title | mFOLFOX-6 | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|---|
| Arm/Group Description | mFOLFOX-6 mFOLFOX-6: Oxaliplatin: 85 per meter squared (mg/m²) IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W |
| Measure Participants | 49 | 52 | 52 |
| Median (95% Confidence Interval) [Weeks] |
53.6
|
41.7
|
42.0
|
| Title | Duration of Response (DoR) |
|---|---|
| Description | DoR was measured from the time measurement criteria are first met for Complete Response or Partial Response or until the first date that the criteria for disease progression or death from any cause. whichever is first recorded. As defined according to RECIST v1.1, CR is the disappearance of all non-nodal target lesions, and PR is the short axes of any target lymph nodes reduced to < 10 mm and at least a 30% decrease in the sum of the diameters of target lesions including the short axes of any target lymph nodes.) |
| Time Frame | Criteria First Met for CR or PR until Disease Progression or Death from Any Cause (Up to 95 Weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population includes all the randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline DoR data. 2 participants were censored in mFOLFOX-6 arm, 2 in mFOLFOX-6 + Ramucirumab arm and 1 in mFOLFOX-6 + Icrucumab. |
| Arm/Group Title | mFOLFOX-6 | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|---|
| Arm/Group Description | mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W(or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV infusion Q2W | mFOLFOX-6 + Ramucirumab IMC-1121B: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab IMC-18F1: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W |
| Measure Participants | 7 | 2 | 2 |
| Median (95% Confidence Interval) [Weeks] |
35.6
|
NA
|
NA
|
| Title | Pharmacokinetics (PK): Maximum Concentration (Cmax) at Cycle 5 |
|---|---|
| Description | Maximum concentration (1 hour post end of infusion, Cmax) is the concentration measured in serum. |
| Time Frame | Cycle 5, 1 Hour Post End of Infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants assigned to the mFOLFOX-6 + Ramucirumab or mFOLFOX-6 + Icrucumab who received at least one dose of study drug and had evaluable ramucirumab or icrucumab PK data to calculate Cmax. |
| Arm/Group Title | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|
| Arm/Group Description | mFOLFOX-6 + Ramucirumab IMC-1121B: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² I.V. infusion q2 weeks (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab IMC-18F1: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² I.V. infusion q2 weeks (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W |
| Measure Participants | 2 | 3 |
| Geometric Mean (Geometric Coefficient of Variation) [microgram/milliliter (µg/mL)] |
NA
(NA)
|
201
(88)
|
| Title | Pharmacokinetics (PK): Trough Serum Concentrations (Ctrough) at Cycle 5 |
|---|---|
| Description | Trough (prior to infusion, Ctrough) concentrations measured in serum. |
| Time Frame | Cycle 5, Prior to Infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants assigned to the mFOLFOX-6 + Ramucirumab or mFOLFOX-6 + Icrucumab who received at least one dose of study drug and had evaluable Ramucirumab or Icrucumab PK data to calculate Ctrough. |
| Arm/Group Title | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|
| Arm/Group Description | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W |
| Measure Participants | 3 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [µg/mL] |
53.6
(123)
|
146
(32)
|
| Title | Maximum Concentration (Cmax) at Day 8 |
|---|---|
| Description | Maximum concentration (Cmax) is the maximum peak concentration measured in blood plasma after drug infusion. |
| Time Frame | Day 8 (cycles 1 and 5) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. Outcome Measure (OM) entered incorrectly and no data collected to report. |
| Arm/Group Title | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|
| Arm/Group Description | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W |
| Measure Participants | 0 | 0 |
| Title | Maximum Concentration (Cmax) at Day 15 |
|---|---|
| Description | Cmax is the maximum peak concentration measured in blood plasma after drug infusion. |
| Time Frame | Day 15 (Cycles 1 and 5) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. OM entered incorrectly and no data collected to report. |
| Arm/Group Title | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|
| Arm/Group Description | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W |
| Measure Participants | 0 | 0 |
| Title | Minimum Concentration (Cmin) at Day 1 |
|---|---|
| Description | Cmin is the minimum peak concentration measured in blood plasma after drug infusion. |
| Time Frame | Day 1 (cycles 1, 5, 9, and 13) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. OM entered incorrectly and no data collected to report. |
| Arm/Group Title | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|
| Arm/Group Description | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W |
| Measure Participants | 0 | 0 |
| Title | Minimum Concentration (Cmin) at Day 4 |
|---|---|
| Description | Cmin is the minimum peak concentration measured in blood plasma after drug infusion. |
| Time Frame | Day 4 (cycles 1 and 5) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. OM entered incorrectly and no data collected to report. |
| Arm/Group Title | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|
| Arm/Group Description | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W |
| Measure Participants | 0 | 0 |
| Title | Minimum Concentration (Cmin) at Day 8 |
|---|---|
| Description | Minimum concentration (Cmin) is the minimum peak concentration measured in blood plasma after drug infusion. |
| Time Frame | Day 8 (cycles 1 and 5) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. OM entered incorrectly and no data collected to report. |
| Arm/Group Title | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|
| Arm/Group Description | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W |
| Measure Participants | 0 | 0 |
| Title | Minimum Concentration (Cmin) at Day 15 |
|---|---|
| Description | Minimum concentration (Cmin) is the minimum peak concentration measured in blood plasma after drug infusion. |
| Time Frame | Day 15 (cycles 1 and 5) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. OM entered incorrectly and no data collected to report. |
| Arm/Group Title | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|
| Arm/Group Description | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² IV Q2W |
| Measure Participants | 0 | 0 |
| Title | Number of Participants With Serum Ramucirumab Antibody Assessment |
|---|---|
| Description | A sample will be considered positive for anti-Ramucirumab antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-Ramucirumab antibody level seen in healthy untreated individuals. |
| Time Frame | 31 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in mFOLFOX-6 +Ramucirumab who received at least one dose of study drug and had at least 1 post treatment assessment. |
| Arm/Group Title | mFOLFOX-6 + Ramucirumab |
|---|---|
| Arm/Group Description | mFOLFOX-6 + Ramucirumab Ramucirumab: 8 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² I.V. infusion q2 weeks (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² I.V. infusion q2 weeks |
| Measure Participants | 52 |
| Count of Participants [Participants] |
0
0%
|
| Title | Serum Anti-Icrucumab Antibody Assessment |
|---|---|
| Description | A sample will be considered positive for anti-icrucumab antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-icrucumab antibody level seen in healthy untreated individuals. |
| Time Frame | 31 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants analyzed. No data collected to report. |
| Arm/Group Title | mFOLFOX-6 + Icrucumab |
|---|---|
| Arm/Group Description | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg IV Q2W mFOLFOX-6: Oxaliplatin: 85 mg/m² IV Q2W FA: 400 mg/m² IV Q2W (or LFA: 200 mg/m² Q2W if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² I.V. infusion Q2W |
| Measure Participants | 0 |
| Title | Number of Participants With Adverse Events |
|---|---|
| Description | A summary of serious AEs (SAEs) and all other non-serious AEs regardless of causality, is located in the Reported Adverse Events module. |
| Time Frame | Baseline up to 165 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population includes all the randomized participants who received at least one dose study drug. |
| Arm/Group Title | mFOLFOX-6 | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab |
|---|---|---|---|
| Arm/Group Description | mFOLFOX-6 mFOLFOX-6: Oxaliplatin: 85 mg/m² I.V. infusion q2 weeks FA: 400 mg/m² I.V. infusion q2 weeks (or LFA: 200 mg/m2 q2 weeks if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² I.V. infusion q2 weeks | mFOLFOX-6 + Ramucirumab IMC-1121B: 8 mg/kg I.V. infusion, administered every 2 weeks mFOLFOX-6: Oxaliplatin: 85 mg/m² I.V. infusion q2 weeks FA: 400 mg/m² I.V. infusion q2 weeks (or LFA: 200 mg/m2 q2 weeks if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² I.V. infusion q2 weeks | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg I.V. infusion, administered every 2 weeks mFOLFOX-6: Oxaliplatin: 85 mg/m² I.V. infusion q2 weeks FA: 400 mg/m² I.V. infusion q2 weeks (or LFA: 200 mg/m2 q2 weeks if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² I.V. infusion q2 weeks |
| Measure Participants | 49 | 52 | 52 |
| Any TEAE |
49
100%
|
52
100%
|
52
100%
|
| Any SAE |
11
22.4%
|
18
34.6%
|
12
23.1%
|
| Any Grade ≥3 AE |
30
61.2%
|
37
71.2%
|
31
59.6%
|
| Any AE leading to discontinuation (any drug) |
6
12.2%
|
18
34.6%
|
11
21.2%
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All randomized participants who received at least one dose of study drug. | |||||
| Arm/Group Title | mFOLFOX-6 | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab | |||
| Arm/Group Description | mFOLFOX-6 mFOLFOX-6: Oxaliplatin: 85 mg/m² I.V. infusion q2 weeks FA: 400 mg/m² I.V. infusion q2 weeks (or LFA: 200 mg/m2 q2 weeks if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² I.V. infusion q2 weeks | mFOLFOX-6 + Ramucirumab Ramucirumab : 8 mg/kg I.V. infusion, administered every 2 weeks mFOLFOX-6: Oxaliplatin: 85 mg/m² I.V. infusion q2 weeks FA: 400 mg/m² I.V. infusion q2 weeks (or LFA: 200 mg/m2 q2 weeks if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² I.V. infusion q2 weeks | mFOLFOX-6 + Icrucumab Icrucumab: 15 mg/kg I.V. infusion, administered every 2 weeks mFOLFOX-6: Oxaliplatin: 85 mg/m² I.V. infusion q2 weeks FA: 400 mg/m² I.V. infusion q2 weeks (or LFA: 200 mg/m2 q2 weeks if FA is unavailable). 5FU: 400 mg/m² bolus + 2400 mg/m² I.V. infusion q2 weeks | |||
All Cause Mortality |
||||||
| mFOLFOX-6 | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 37/49 (75.5%) | 41/52 (78.8%) | 40/52 (76.9%) | |||
Serious Adverse Events |
||||||
| mFOLFOX-6 | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/49 (22.4%) | 18/52 (34.6%) | 12/52 (23.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 1/49 (2%) | 1 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Neutropenia | 0/49 (0%) | 0 | 0/52 (0%) | 0 | 1/52 (1.9%) | 1 |
| Cardiac disorders | ||||||
| Acute myocardial infarction | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Eye disorders | ||||||
| Cataract | 1/49 (2%) | 1 | 0/52 (0%) | 0 | 0/52 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/49 (2%) | 1 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Constipation | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Diarrhoea | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Intestinal perforation | 0/49 (0%) | 0 | 0/52 (0%) | 0 | 1/52 (1.9%) | 1 |
| Large intestine perforation | 1/49 (2%) | 1 | 0/52 (0%) | 0 | 0/52 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Nausea | 1/49 (2%) | 1 | 0/52 (0%) | 0 | 1/52 (1.9%) | 1 |
| Peritonitis | 0/49 (0%) | 0 | 0/52 (0%) | 0 | 1/52 (1.9%) | 1 |
| Proctalgia | 0/49 (0%) | 0 | 0/52 (0%) | 0 | 1/52 (1.9%) | 1 |
| Small intestinal obstruction | 1/49 (2%) | 1 | 0/52 (0%) | 0 | 0/52 (0%) | 0 |
| Vomiting | 2/49 (4.1%) | 2 | 0/52 (0%) | 0 | 2/52 (3.8%) | 2 |
| General disorders | ||||||
| Fatigue | 0/49 (0%) | 0 | 2/52 (3.8%) | 2 | 1/52 (1.9%) | 1 |
| Infusion related reaction | 1/49 (2%) | 1 | 0/52 (0%) | 0 | 0/52 (0%) | 0 |
| Pyrexia | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 3/52 (5.8%) | 3 |
| Hepatobiliary disorders | ||||||
| Bile duct obstruction | 0/49 (0%) | 0 | 2/52 (3.8%) | 2 | 0/52 (0%) | 0 |
| Bile duct stenosis | 1/49 (2%) | 1 | 0/52 (0%) | 0 | 0/52 (0%) | 0 |
| Hepatic failure | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Infections and infestations | ||||||
| Cystitis | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Device related infection | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Enterocolitis infectious | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Neutropenic infection | 1/49 (2%) | 1 | 0/52 (0%) | 0 | 0/52 (0%) | 0 |
| Sepsis | 2/49 (4.1%) | 2 | 0/52 (0%) | 0 | 1/52 (1.9%) | 1 |
| Urinary tract infection | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Medication error | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Stent occlusion | 0/49 (0%) | 0 | 0/52 (0%) | 0 | 1/52 (1.9%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/49 (0%) | 0 | 0/52 (0%) | 0 | 2/52 (3.8%) | 2 |
| Diabetic ketoacidosis | 0/49 (0%) | 0 | 0/52 (0%) | 0 | 2/52 (3.8%) | 2 |
| Hypokalaemia | 0/49 (0%) | 0 | 0/52 (0%) | 0 | 1/52 (1.9%) | 1 |
| Hyponatraemia | 0/49 (0%) | 0 | 1/52 (1.9%) | 2 | 0/52 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Muscular weakness | 0/49 (0%) | 0 | 0/52 (0%) | 0 | 1/52 (1.9%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Neoplasm progression | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 1/52 (1.9%) | 1 |
| Nervous system disorders | ||||||
| Cerebrovascular accident | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Hydronephrosis | 1/49 (2%) | 1 | 0/52 (0%) | 0 | 0/52 (0%) | 0 |
| Nephrotic syndrome | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Renal failure acute | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Ureteric obstruction | 1/49 (2%) | 1 | 0/52 (0%) | 0 | 0/52 (0%) | 0 |
| Urinary retention | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
| Pleural effusion | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 1/52 (1.9%) | 2 |
| Pulmonary embolism | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 1/52 (1.9%) | 1 |
| Vascular disorders | ||||||
| Embolism | 0/49 (0%) | 0 | 1/52 (1.9%) | 1 | 0/52 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| mFOLFOX-6 | mFOLFOX-6 + Ramucirumab | mFOLFOX-6 + Icrucumab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 48/49 (98%) | 52/52 (100%) | 52/52 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 9/49 (18.4%) | 12 | 7/52 (13.5%) | 19 | 12/52 (23.1%) | 33 |
| Neutropenia | 16/49 (32.7%) | 37 | 16/52 (30.8%) | 39 | 12/52 (23.1%) | 19 |
| Thrombocytopenia | 12/49 (24.5%) | 35 | 9/52 (17.3%) | 37 | 3/52 (5.8%) | 5 |
| Cardiac disorders | ||||||
| Sinus tachycardia | 0/49 (0%) | 0 | 0/52 (0%) | 0 | 3/52 (5.8%) | 4 |
| Eye disorders | ||||||
| Lacrimation increased | 3/49 (6.1%) | 4 | 2/52 (3.8%) | 2 | 8/52 (15.4%) | 9 |
| Vision blurred | 2/49 (4.1%) | 2 | 1/52 (1.9%) | 1 | 5/52 (9.6%) | 6 |
| Gastrointestinal disorders | ||||||
| Abdominal distension | 3/49 (6.1%) | 3 | 6/52 (11.5%) | 10 | 9/52 (17.3%) | 10 |
| Abdominal pain | 13/49 (26.5%) | 21 | 16/52 (30.8%) | 20 | 24/52 (46.2%) | 37 |
| Abdominal pain upper | 1/49 (2%) | 1 | 3/52 (5.8%) | 3 | 0/52 (0%) | 0 |
| Ascites | 2/49 (4.1%) | 2 | 6/52 (11.5%) | 11 | 8/52 (15.4%) | 9 |
| Constipation | 12/49 (24.5%) | 21 | 18/52 (34.6%) | 27 | 19/52 (36.5%) | 32 |
| Diarrhoea | 19/49 (38.8%) | 53 | 30/52 (57.7%) | 54 | 27/52 (51.9%) | 68 |
| Dry mouth | 2/49 (4.1%) | 5 | 3/52 (5.8%) | 3 | 1/52 (1.9%) | 1 |
| Dyspepsia | 7/49 (14.3%) | 11 | 2/52 (3.8%) | 2 | 1/52 (1.9%) | 1 |
| Flatulence | 2/49 (4.1%) | 2 | 0/52 (0%) | 0 | 6/52 (11.5%) | 6 |
| Gastrooesophageal reflux disease | 2/49 (4.1%) | 2 | 4/52 (7.7%) | 4 | 0/52 (0%) | 0 |
| Gingival bleeding | 0/49 (0%) | 0 | 5/52 (9.6%) | 5 | 2/52 (3.8%) | 3 |
| Nausea | 30/49 (61.2%) | 61 | 24/52 (46.2%) | 42 | 36/52 (69.2%) | 82 |
| Proctalgia | 5/49 (10.2%) | 5 | 2/52 (3.8%) | 2 | 0/52 (0%) | 0 |
| Stomatitis | 12/49 (24.5%) | 30 | 19/52 (36.5%) | 30 | 12/52 (23.1%) | 19 |
| Toothache | 0/49 (0%) | 0 | 6/52 (11.5%) | 6 | 1/52 (1.9%) | 1 |
| Vomiting | 17/49 (34.7%) | 31 | 13/52 (25%) | 21 | 27/52 (51.9%) | 58 |
| General disorders | ||||||
| Asthenia | 0/49 (0%) | 0 | 5/52 (9.6%) | 6 | 2/52 (3.8%) | 2 |
| Chills | 4/49 (8.2%) | 4 | 1/52 (1.9%) | 1 | 2/52 (3.8%) | 2 |
| Face oedema | 0/49 (0%) | 0 | 2/52 (3.8%) | 2 | 13/52 (25%) | 15 |
| Fatigue | 35/49 (71.4%) | 86 | 45/52 (86.5%) | 91 | 36/52 (69.2%) | 106 |
| Infusion related reaction | 5/49 (10.2%) | 19 | 7/52 (13.5%) | 9 | 3/52 (5.8%) | 7 |
| Mucosal inflammation | 1/49 (2%) | 1 | 3/52 (5.8%) | 3 | 0/52 (0%) | 0 |
| Non-cardiac chest pain | 2/49 (4.1%) | 2 | 3/52 (5.8%) | 5 | 1/52 (1.9%) | 1 |
| Oedema peripheral | 5/49 (10.2%) | 13 | 15/52 (28.8%) | 28 | 29/52 (55.8%) | 54 |
| Pyrexia | 11/49 (22.4%) | 12 | 9/52 (17.3%) | 13 | 8/52 (15.4%) | 11 |
| Temperature intolerance | 21/49 (42.9%) | 76 | 13/52 (25%) | 33 | 18/52 (34.6%) | 66 |
| Infections and infestations | ||||||
| Oral candidiasis | 0/49 (0%) | 0 | 3/52 (5.8%) | 4 | 2/52 (3.8%) | 2 |
| Sinusitis | 0/49 (0%) | 0 | 3/52 (5.8%) | 3 | 0/52 (0%) | 0 |
| Upper respiratory tract infection | 1/49 (2%) | 1 | 5/52 (9.6%) | 5 | 1/52 (1.9%) | 1 |
| Urinary tract infection | 1/49 (2%) | 1 | 3/52 (5.8%) | 4 | 1/52 (1.9%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Contusion | 2/49 (4.1%) | 2 | 2/52 (3.8%) | 2 | 3/52 (5.8%) | 3 |
| Investigations | ||||||
| Aspartate aminotransferase increased | 6/49 (12.2%) | 7 | 3/52 (5.8%) | 6 | 4/52 (7.7%) | 8 |
| Blood alkaline phosphatase increased | 6/49 (12.2%) | 10 | 5/52 (9.6%) | 7 | 2/52 (3.8%) | 5 |
| Lymphocyte count decreased | 2/49 (4.1%) | 9 | 1/52 (1.9%) | 3 | 3/52 (5.8%) | 14 |
| Neutrophil count decreased | 7/49 (14.3%) | 12 | 5/52 (9.6%) | 9 | 5/52 (9.6%) | 7 |
| Platelet count decreased | 3/49 (6.1%) | 16 | 8/52 (15.4%) | 50 | 4/52 (7.7%) | 10 |
| Weight decreased | 7/49 (14.3%) | 8 | 14/52 (26.9%) | 18 | 4/52 (7.7%) | 9 |
| White blood cell count decreased | 3/49 (6.1%) | 8 | 4/52 (7.7%) | 6 | 3/52 (5.8%) | 6 |
| Metabolism and nutrition disorders | ||||||
| Anorexia | 16/49 (32.7%) | 29 | 20/52 (38.5%) | 26 | 27/52 (51.9%) | 46 |
| Decreased appetite | 3/49 (6.1%) | 3 | 1/52 (1.9%) | 2 | 3/52 (5.8%) | 3 |
| Dehydration | 3/49 (6.1%) | 4 | 6/52 (11.5%) | 13 | 6/52 (11.5%) | 9 |
| Hyperglycaemia | 2/49 (4.1%) | 4 | 3/52 (5.8%) | 3 | 2/52 (3.8%) | 4 |
| Hypoalbuminaemia | 3/49 (6.1%) | 7 | 4/52 (7.7%) | 7 | 7/52 (13.5%) | 16 |
| Hypokalaemia | 4/49 (8.2%) | 5 | 3/52 (5.8%) | 3 | 9/52 (17.3%) | 14 |
| Hypomagnesaemia | 3/49 (6.1%) | 8 | 2/52 (3.8%) | 2 | 6/52 (11.5%) | 6 |
| Hyponatraemia | 2/49 (4.1%) | 5 | 4/52 (7.7%) | 10 | 3/52 (5.8%) | 7 |
| Hypophosphataemia | 3/49 (6.1%) | 3 | 0/52 (0%) | 0 | 2/52 (3.8%) | 3 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 3/49 (6.1%) | 4 | 3/52 (5.8%) | 4 | 6/52 (11.5%) | 10 |
| Back pain | 7/49 (14.3%) | 14 | 8/52 (15.4%) | 9 | 7/52 (13.5%) | 11 |
| Flank pain | 4/49 (8.2%) | 5 | 0/52 (0%) | 0 | 1/52 (1.9%) | 1 |
| Muscular weakness | 4/49 (8.2%) | 4 | 2/52 (3.8%) | 3 | 3/52 (5.8%) | 5 |
| Musculoskeletal chest pain | 1/49 (2%) | 1 | 0/52 (0%) | 0 | 3/52 (5.8%) | 3 |
| Myalgia | 0/49 (0%) | 0 | 1/52 (1.9%) | 3 | 4/52 (7.7%) | 4 |
| Pain in extremity | 5/49 (10.2%) | 7 | 1/52 (1.9%) | 2 | 1/52 (1.9%) | 1 |
| Pain in jaw | 5/49 (10.2%) | 9 | 0/52 (0%) | 0 | 3/52 (5.8%) | 8 |
| Nervous system disorders | ||||||
| Dizziness | 2/49 (4.1%) | 3 | 7/52 (13.5%) | 9 | 6/52 (11.5%) | 6 |
| Dysaesthesia | 3/49 (6.1%) | 5 | 7/52 (13.5%) | 27 | 4/52 (7.7%) | 6 |
| Dysgeusia | 5/49 (10.2%) | 5 | 6/52 (11.5%) | 9 | 17/52 (32.7%) | 21 |
| Headache | 8/49 (16.3%) | 12 | 16/52 (30.8%) | 29 | 9/52 (17.3%) | 12 |
| Memory impairment | 1/49 (2%) | 2 | 3/52 (5.8%) | 3 | 1/52 (1.9%) | 1 |
| Neuropathy peripheral | 12/49 (24.5%) | 22 | 12/52 (23.1%) | 23 | 10/52 (19.2%) | 13 |
| Paraesthesia | 2/49 (4.1%) | 4 | 3/52 (5.8%) | 11 | 5/52 (9.6%) | 6 |
| Peripheral sensory neuropathy | 27/49 (55.1%) | 94 | 25/52 (48.1%) | 72 | 32/52 (61.5%) | 81 |
| Psychiatric disorders | ||||||
| Depression | 0/49 (0%) | 0 | 3/52 (5.8%) | 3 | 1/52 (1.9%) | 1 |
| Insomnia | 7/49 (14.3%) | 8 | 7/52 (13.5%) | 8 | 10/52 (19.2%) | 13 |
| Renal and urinary disorders | ||||||
| Proteinuria | 1/49 (2%) | 1 | 6/52 (11.5%) | 11 | 1/52 (1.9%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 9/49 (18.4%) | 10 | 16/52 (30.8%) | 19 | 10/52 (19.2%) | 11 |
| Dysphonia | 2/49 (4.1%) | 3 | 4/52 (7.7%) | 7 | 2/52 (3.8%) | 2 |
| Dyspnoea | 4/49 (8.2%) | 6 | 10/52 (19.2%) | 13 | 16/52 (30.8%) | 20 |
| Dyspnoea exertional | 1/49 (2%) | 3 | 2/52 (3.8%) | 2 | 3/52 (5.8%) | 4 |
| Epistaxis | 5/49 (10.2%) | 6 | 14/52 (26.9%) | 17 | 3/52 (5.8%) | 5 |
| Nasal congestion | 1/49 (2%) | 1 | 1/52 (1.9%) | 1 | 3/52 (5.8%) | 4 |
| Oropharyngeal pain | 1/49 (2%) | 1 | 2/52 (3.8%) | 2 | 6/52 (11.5%) | 6 |
| Pleural effusion | 0/49 (0%) | 0 | 3/52 (5.8%) | 3 | 2/52 (3.8%) | 2 |
| Productive cough | 4/49 (8.2%) | 4 | 2/52 (3.8%) | 2 | 2/52 (3.8%) | 3 |
| Rhinorrhoea | 1/49 (2%) | 1 | 0/52 (0%) | 0 | 3/52 (5.8%) | 4 |
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 5/49 (10.2%) | 6 | 0/52 (0%) | 0 | 1/52 (1.9%) | 2 |
| Dry skin | 3/49 (6.1%) | 4 | 1/52 (1.9%) | 1 | 5/52 (9.6%) | 5 |
| Erythema | 0/49 (0%) | 0 | 0/52 (0%) | 0 | 4/52 (7.7%) | 10 |
| Palmar-plantar erythrodysaesthesia syndrome | 3/49 (6.1%) | 5 | 6/52 (11.5%) | 10 | 1/52 (1.9%) | 1 |
| Periorbital oedema | 0/49 (0%) | 0 | 0/52 (0%) | 0 | 6/52 (11.5%) | 7 |
| Pruritus | 3/49 (6.1%) | 4 | 4/52 (7.7%) | 5 | 2/52 (3.8%) | 3 |
| Rash | 3/49 (6.1%) | 5 | 15/52 (28.8%) | 22 | 8/52 (15.4%) | 9 |
| Skin hyperpigmentation | 3/49 (6.1%) | 4 | 3/52 (5.8%) | 3 | 1/52 (1.9%) | 2 |
| Vascular disorders | ||||||
| Flushing | 1/49 (2%) | 1 | 2/52 (3.8%) | 3 | 3/52 (5.8%) | 3 |
| Hypertension | 1/49 (2%) | 1 | 15/52 (28.8%) | 24 | 5/52 (9.6%) | 8 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Compnay |
| Phone | 800-545-5979 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01111604
Other Study ID Numbers:
- 13942
- CP20-0801
- I4Y-IE-JCDB
First Posted:
Apr 27, 2010
Last Update Posted:
Aug 6, 2019
Last Verified:
Jul 1, 2019