A Study of IMC-1121B or IMC-18F1 in Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01111604
First received: April 8, 2010
Last updated: April 28, 2014
Last verified: April 2014

April 8, 2010
April 28, 2014
August 2010
December 2013   (final data collection date for primary outcome measure)
Progression-free survival (PFS) [ Time Frame: 31 Weeks ] [ Designated as safety issue: No ]
PFS is defined as the time from the date of randomization until the date of objectively determined progression as defined by RECIST v1.1, or death from any cause, whichever is first.
Progression-free survival (PFS) [ Time Frame: Every 8 weeks from the date of enrollment to the first date of progressive disease or death due to any cause ] [ Designated as safety issue: No ]
PFS is defined as the time from the date of randomization until the date of objectively determined progression as defined by RECIST v1.1, or death from any cause, whichever is first.
Complete list of historical versions of study NCT01111604 on ClinicalTrials.gov Archive Site
  • Objective response rate (ORR) [ Time Frame: 31 Weeks ] [ Designated as safety issue: No ]
    The ORR is the proportion of all randomized patients with Partial Response (PR) or Complete Response (CR) according to RECIST v1.1 from the start of the treatment until disease progression/recurrence
  • Overall survival (OS) [ Time Frame: 31 Weeks ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from the date of randomization to the date of death from any cause. If the patient 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 patient is known to be alive.
  • Duration of response [ Time Frame: 31 Weeks ] [ Designated as safety issue: No ]
    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 PD is met (taking as a reference for PD that smallest measurement recorded since the treatment started), or death, is objectively documented.
  • Maximum concentration (Cmax) at Day 1 [ Time Frame: Day 1 (cycles 1, 5, 9, and 13) ] [ Designated as safety issue: No ]
    Maximum concentration (Cmax) is the maximum peak concentration measured in blood plasma after drug infusion.
  • Maximum concentration (Cmax) at Day 4 [ Time Frame: Day 4 (cycles 1 and 5) ] [ Designated as safety issue: No ]
    Maximum concentration (Cmax) is the maximum peak concentration measured in blood plasma after drug infusion.
  • Maximum concentration (Cmax) at Day 8 [ Time Frame: Day 8 (cycles 1 and 5) ] [ Designated as safety issue: No ]
    Maximum concentration (Cmax) is the maximum peak concentration measured in blood plasma after drug infusion.
  • Maximum concentration (Cmax) at Day 15 [ Time Frame: Day 15 (cycles 1 and 5) ] [ Designated as safety issue: No ]
    Maximum concentration (Cmax) is the maximum peak concentration measured in blood plasma after drug infusion.
  • Minimum concentration (Cmin) at Day 1 [ Time Frame: Day 1 (cycles 1, 5, 9, and 13) ] [ Designated as safety issue: No ]
    Minimum concentration (Cmin) is the minimum peak concentration measured in blood plasma after drug infusion.
  • Minimum concentration (Cmin) at Day 4 [ Time Frame: Day 4 (cycles 1 and 5) ] [ Designated as safety issue: No ]
    Minimum concentration (Cmin) is the minimum peak concentration measured in blood plasma after drug infusion.
  • Minimum concentration (Cmin) at Day 8 [ Time Frame: Day 8 (cycles 1 and 5) ] [ Designated as safety issue: No ]
    Minimum concentration (Cmin) is the minimum peak concentration measured in blood plasma after drug infusion.
  • Minimum concentration (Cmin) at Day 15 [ Time Frame: Day 15 (cycles 1 and 5) ] [ Designated as safety issue: No ]
    Minimum concentration (Cmin) is the minimum peak concentration measured in blood plasma after drug infusion.
  • Serum Anti-1121B Antibody Assessment [ Time Frame: 31 Weeks ] [ Designated as safety issue: Yes ]
    A sample will be considered positive for anti-IMC-1121B antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-IMC-1121B antibody level seen in healthy untreated individuals.
  • Serum Anti-IMC-18F1 Antibody Assessment [ Time Frame: 31 Weeks ] [ Designated as safety issue: Yes ]
    A sample will be considered positive for anti-IMC-18F1 antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-IMC-18F1 antibody level seen in healthy untreated individuals.
  • Number of Participants with Adverse Events [ Time Frame: 31 Weeks ] [ Designated as safety issue: Yes ]
  • Objective response rate (ORR) [ Time Frame: Every 8 weeks from the start of the first dose of study medication. ] [ Designated as safety issue: No ]
    The ORR is the proportion of all randomized patients with Partial Response (PR) or Complete Response (CR) according to RECIST v1.1 from the start of the treatment until disease progression/recurrence
  • Overall survival (OS) [ Time Frame: Every 8 weeks from the date of randomization to the date of death from any cause. ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from the date of randomization to the date of death from any cause. If the patient 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 patient is known to be alive.
  • Duration of response [ Time Frame: Every 8 weeks from the start of the first dose of study medication. ] [ Designated as safety issue: No ]
    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 PD is met (taking as a reference for PD that smallest measurement recorded since the treatment started), or death, is objectively documented.
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability of IMC-1121B [ Time Frame: Every 2 weeks from the start of the first dose of study medication. ] [ Designated as safety issue: Yes ]
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability of IMC-18F1 [ Time Frame: Every 2 weeks from the start of the first dose of study medication. ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters to assess serum IMC-1121B. [ Time Frame: 27 Weeks ] [ Designated as safety issue: No ]
    Maximum plasma concentration of IMC-1121B: Day 1, Cycle 1; Day 4, Cycle 1; Day 8, Cycle 1; and Day 15, Cycle 1.
  • Pharmacokinetic parameters to assess serum IMC-18F1. [ Time Frame: 27 Weeks ] [ Designated as safety issue: No ]
    Maximum plasma concentration of IMC-1121B: Day 1, Cycle 1; Day 4, Cycle 1; Day 8, Cycle 1; and Day 15, Cycle 1.
  • Pharmacodynamics of IMC-1121B [ Time Frame: 31 Weeks ] [ Designated as safety issue: Yes ]
    Blood samples obtained will be assayed to determine circulating levels for VEGF, soluble VEGFR 1, and soluble VEGFR-2.
  • Pharmacodynamics of IMC-11F8 [ Time Frame: 31 Weeks ] [ Designated as safety issue: No ]
    Blood samples obtained will be assayed to determine circulating levels for VEGF, soluble VEGFR 1, and soluble VEGFR-2.
  • Immunogenicity of IMC-1121B [ Time Frame: 31 Weeks ] [ Designated as safety issue: Yes ]
    A sample will be considered positive for anti-IMC-1121B antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-IMC-1121B antibody level seen in healthy untreated individuals.
  • Immunogenicity of IMC-11F8 [ Time Frame: 31 Weeks ] [ Designated as safety issue: Yes ]
    A sample will be considered positive for anti-IMC-11F8 antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-IMC-11F8 antibody level seen in healthy untreated individuals.
Not Provided
Not Provided
 
A Study of IMC-1121B or IMC-18F1 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 IMC-1121B 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 patients with metastatic colorectal cancer live longer without their cancer progressing when treated with standard chemotherapy, standard chemotherapy plus IMC-1121B, or standard chemotherapy plus IMC-18F1.

The purpose of this study is to evaluate the progression-free survival (PFS) in patients 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 patient care.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Colon Cancer
  • Rectal Cancer
  • Biological: IMC-1121B
    8 mg/kg I.V. infusion, administered every 2 weeks
    Other Names:
    • Ramucirumab
    • LY3009806
  • Biological: IMC-18F1
    15 mg/kg I.V. infusion, administered every 2 weeks
    Other Name: LY3012212
  • Drug: 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

  • Active Comparator: mFOLFOX-6
    mFOLFOX-6
    Intervention: Drug: mFOLFOX-6
  • Experimental: mFOLFOX-6 + IMC-1121B
    mFOLFOX-6 + IMC-1121B
    Interventions:
    • Biological: IMC-1121B
    • Drug: mFOLFOX-6
  • Experimental: mFOLFOX-6 + IMC-18F1
    mFOLFOX-6 + IMC-18F1
    Interventions:
    • Biological: IMC-18F1
    • Drug: mFOLFOX-6
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
157
December 2013
December 2013   (final data collection date for primary outcome measure)

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
  • ECOG PS (Eastern Cooperative Oncology Group Performance Status) 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 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 patient 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 patient 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01111604
13942, CP20-0801, I4Y-IE-JCDB
Yes
Eli Lilly and Company
Eli Lilly and Company
Not Provided
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
Eli Lilly and Company
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP