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
  Purpose

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.


Condition Intervention Phase
Colon Cancer
Rectal Cancer
Biological: IMC-1121B
Biological: IMC-18F1
Drug: mFOLFOX-6
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 157
Study Start Date: August 2010
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: mFOLFOX-6
mFOLFOX-6
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

Experimental: mFOLFOX-6 + IMC-1121B
mFOLFOX-6 + IMC-1121B
Biological: IMC-1121B
8 mg/kg I.V. infusion, administered every 2 weeks
Other Names:
  • Ramucirumab
  • LY3009806
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

Experimental: mFOLFOX-6 + IMC-18F1
mFOLFOX-6 + IMC-18F1
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


Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01111604

Locations
United States, Ohio
ImClone Investigational Site
Cincinnati, Ohio, United States, 45242
United States, South Carolina
ImClone Investigational Site
Columbia, South Carolina, United States, 29210
United States, Tennessee
ImClone Investigational Site
Nashville, Tennessee, United States, 37232
Canada, Alberta
ImClone Investigational Site
Calgary, Alberta, Canada, T2N 4N2
ImClone Investigational Site
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
ImClone Investigational Site
Kelowna, British Columbia, Canada, V1Y 5L3
ImClone Investigational Site
Surrey, British Columbia, Canada, V3V 1Z2
ImClone Investigational Site
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Nova Scotia
ImClone Investigational Site
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
ImClone Investigational Site
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
Canada, Quebec
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01111604     History of Changes
Other Study ID Numbers: 13942, CP20-0801, I4Y-IE-JCDB
Study First Received: April 8, 2010
Last Updated: April 28, 2014
Health Authority: Canada: Health Canada
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Eli Lilly and Company:
Colonic Neoplasms
Rectal Neoplasms
Adenocarcinoma
Antibodies, Monoclonal

Additional relevant MeSH terms:
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on August 28, 2014