A Study of Ramucirumab or Icrucumab in Colorectal Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Rectal Cancer; Colon Cancer
• Intervention / Treatment: Drug: mFOLFOX-6; Biological: Ramucirumab; Biological: 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.

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • ImClone Investigational Site
    • Edmonton, Alberta, Canada, T6G 1Z2
      • ImClone Investigational Site
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • ImClone Investigational Site
    • Surrey, British Columbia, Canada, V3V 1Z2
      • ImClone Investigational Site
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • ImClone Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • ImClone Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • ImClone Investigational Site
    • London, Ontario, Canada, N6A 4L6
      • ImClone Investigational Site
    • Mississauga, Ontario, Canada, L5M 2N1
      • ImClone Investigational Site
    • Oshawa, Ontario, Canada, L1G 2B9
      • ImClone Investigational Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • ImClone Investigational Site
    • Toronto, Ontario, Canada, M5G 2M9
      • ImClone Investigational Site
    • Windsor, Ontario, Canada, N8W 2X3
      • ImClone Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H2W 156
      • ImClone Investigational Site
• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • ImClone Investigational Site
  • South Carolina
    • Columbia, South Carolina, United States, 29210
      • ImClone Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • ImClone Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	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; Biological: Ramucirumab; 8 mg/kg IV Q2W; Other Names: LY3009806; IMC-1121B
Experimental: mFOLFOX-6 + Icrucumab	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; Biological: Icrucumab; 15 mg/kg IV Q2W; Other Names: IMC-18F1; LY3012212

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline until Disease Progression or Death from Any Cause (Up to 95 Weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline until Disease Progression (Up to 95 Weeks)
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.	Baseline Until Death from Any Cause (Up to 163 Weeks)
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.)	Criteria First Met for CR or PR until Disease Progression or Death from Any Cause (Up to 95 Weeks)
Pharmacokinetics (PK): Maximum Concentration (Cmax) at Cycle 5	Maximum concentration (1 hour post end of infusion, Cmax) is the concentration measured in serum.	Cycle 5, 1 Hour Post End of Infusion
Pharmacokinetics (PK): Trough Serum Concentrations (Ctrough) at Cycle 5	Trough (prior to infusion, Ctrough) concentrations measured in serum.	Cycle 5, Prior to Infusion
Maximum Concentration (Cmax) at Day 8	Maximum concentration (Cmax) is the maximum peak concentration measured in blood plasma after drug infusion.	Day 8 (cycles 1 and 5)
Maximum Concentration (Cmax) at Day 15	Cmax is the maximum peak concentration measured in blood plasma after drug infusion.	Day 15 (Cycles 1 and 5)
Minimum Concentration (Cmin) at Day 1	Cmin is the minimum peak concentration measured in blood plasma after drug infusion.	Day 1 (cycles 1, 5, 9, and 13)
Minimum Concentration (Cmin) at Day 4	Cmin is the minimum peak concentration measured in blood plasma after drug infusion.	Day 4 (cycles 1 and 5)
Minimum Concentration (Cmin) at Day 8	Minimum concentration (Cmin) is the minimum peak concentration measured in blood plasma after drug infusion.	Day 8 (cycles 1 and 5)
Minimum Concentration (Cmin) at Day 15	Minimum concentration (Cmin) is the minimum peak concentration measured in blood plasma after drug infusion.	Day 15 (cycles 1 and 5)
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.	31 Weeks
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.	31 Weeks
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.	Baseline up to 165 weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: April 8, 2010
• First Submitted That Met QC Criteria: April 26, 2010
• First Posted (Estimate): April 27, 2010

Study Record Updates

• Last Update Posted (Actual): August 6, 2019
• Last Update Submitted That Met QC Criteria: July 15, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Adenocarcinoma; Antibodies, Monoclonal; Rectal Neoplasms; Colonic Neoplasms
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Ramucirumab
• Other Study ID Numbers: 13942; CP20-0801 (Other Identifier: ImClone Systems); I4Y-IE-JCDB (Other Identifier: Eli Lilly and Company)