Back to resultsA Study of Ramucirumab or Icrucumab in Colorectal Cancer
Primary Purpose
Colon Cancer, Rectal Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ramucirumab
Icrucumab
mFOLFOX-6
Sponsored by
About this trial
This is an interventional treatment trial for Colon Cancer focused on measuring Colonic Neoplasms, Rectal Neoplasms, Adenocarcinoma, Antibodies, Monoclonal
Eligibility Criteria
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
Sites / Locations
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
mFOLFOX-6
mFOLFOX-6 + Ramucirumab
mFOLFOX-6 + Icrucumab
Arm Description
mFOLFOX-6
mFOLFOX-6 + Ramucirumab
mFOLFOX-6 + Icrucumab
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS)
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])
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)
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)
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
Maximum concentration (1 hour post end of infusion, Cmax) is the concentration measured in serum.
Pharmacokinetics (PK): Trough Serum Concentrations (Ctrough) at Cycle 5
Trough (prior to infusion, Ctrough) concentrations measured in serum.
Maximum Concentration (Cmax) at Day 8
Maximum concentration (Cmax) is the maximum peak concentration measured in blood plasma after drug infusion.
Maximum Concentration (Cmax) at Day 15
Cmax is the maximum peak concentration measured in blood plasma after drug infusion.
Minimum Concentration (Cmin) at Day 1
Cmin is the minimum peak concentration measured in blood plasma after drug infusion.
Minimum Concentration (Cmin) at Day 4
Cmin is the minimum peak concentration measured in blood plasma after drug infusion.
Minimum Concentration (Cmin) at Day 8
Minimum concentration (Cmin) is the minimum peak concentration measured in blood plasma after drug infusion.
Minimum Concentration (Cmin) at Day 15
Minimum concentration (Cmin) is the minimum peak concentration measured in blood plasma after drug infusion.
Number of Participants With Serum Ramucirumab Antibody Assessment
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
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
A summary of serious AEs (SAEs) and all other non-serious AEs regardless of causality, is located in the Reported Adverse Events module.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01111604
Brief Title
A Study of Ramucirumab or Icrucumab in Colorectal Cancer
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 Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colon Cancer, Rectal Cancer
Keywords
Colonic Neoplasms, Rectal Neoplasms, Adenocarcinoma, Antibodies, Monoclonal
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
158 (Actual)
8. Arms, Groups, and Interventions
Arm Title
mFOLFOX-6
Arm Type
Active Comparator
Arm Description
mFOLFOX-6
Arm Title
mFOLFOX-6 + Ramucirumab
Arm Type
Experimental
Arm Description
mFOLFOX-6 + Ramucirumab
Arm Title
mFOLFOX-6 + Icrucumab
Arm Type
Experimental
Arm Description
mFOLFOX-6 + Icrucumab
Intervention Type
Biological
Intervention Name(s)
Ramucirumab
Other Intervention Name(s)
IMC-1121B, LY3009806
Intervention Description
8 mg/kg IV Q2W
Intervention Type
Biological
Intervention Name(s)
Icrucumab
Other Intervention Name(s)
IMC-18F1, LY3012212
Intervention Description
15 mg/kg IV Q2W
Intervention Type
Drug
Intervention Name(s)
mFOLFOX-6
Intervention Description
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
Primary Outcome Measure Information:
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)
Secondary Outcome Measure Information:
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)
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)
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)
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
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
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)
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)
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)
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)
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)
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)
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
ImClone Investigational Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
ImClone Investigational Site
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29210
Country
United States
Facility Name
ImClone Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
ImClone Investigational Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
ImClone Investigational Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
ImClone Investigational Site
City
Kelowna
State/Province
British Columbia
ZIP/Postal Code
V1Y 5L3
Country
Canada
Facility Name
ImClone Investigational Site
City
Surrey
State/Province
British Columbia
ZIP/Postal Code
V3V 1Z2
Country
Canada
Facility Name
ImClone Investigational Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
ImClone Investigational Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V7
Country
Canada
Facility Name
ImClone Investigational Site
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
ImClone Investigational Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
ImClone Investigational Site
City
Mississauga
State/Province
Ontario
ZIP/Postal Code
L5M 2N1
Country
Canada
Facility Name
ImClone Investigational Site
City
Oshawa
State/Province
Ontario
ZIP/Postal Code
L1G 2B9
Country
Canada
Facility Name
ImClone Investigational Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
ImClone Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
ImClone Investigational Site
City
Windsor
State/Province
Ontario
ZIP/Postal Code
N8W 2X3
Country
Canada
Facility Name
ImClone Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 156
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
27733377
Citation
Moore M, Gill S, Asmis T, Berry S, Burkes R, Zbuk K, Alcindor T, Jeyakumar A, Chan T, Rao S, Spratlin J, Tang PA, Rothenstein J, Chan E, Bendell J, Kudrik F, Kauh J, Tang S, Gao L, Kambhampati SR, Nasroulah F, Yang L, Ramdas N, Binder P, Strevel E. Randomized phase II study of modified FOLFOX-6 in combination with ramucirumab or icrucumab as second-line therapy in patients with metastatic colorectal cancer after disease progression on first-line irinotecan-based therapy. Ann Oncol. 2016 Dec;27(12):2216-2224. doi: 10.1093/annonc/mdw412. Epub 2016 Oct 11.
Results Reference
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A Study of Ramucirumab or Icrucumab in Colorectal Cancer
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