A Study of IMC-1121B in Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00862784
First received: March 16, 2009
Last updated: August 14, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to test how long patients with colorectal cancer live without progressive disease when being treated with IMC-1121B and the modified FOLFOX-6 chemotherapy.


Condition Intervention Phase
Colorectal Carcinoma
Biological: IMC-1121B (ramucirumab)
Drug: Oxaliplatin
Drug: Folinic acid
Drug: 5-FU
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Multicenter, Phase 2 Study Evaluating the Safety and Efficacy of IMC-1121B in Combination With 5-FU/FA and Oxaliplatin (Modified FOLFOX-6) as First-line Therapy in Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: Approximately 28 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: Approximately 28 Months ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Approximately 28 Months ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Approximately 28 Months ] [ Designated as safety issue: No ]
  • Number of Participants with Adverse Events (AEs) [ Time Frame: Approximately 28 Months ] [ Designated as safety issue: Yes ]
  • Number of Participants with Severe Adverse Events (SAEs) [ Time Frame: Approximately 28 Months ] [ Designated as safety issue: Yes ]
  • Maximum concentration (Cmax) at Day 1 [ Time Frame: Day 1 (Cycle 1) ] [ Designated as safety issue: No ]
    Evaluated at Baseline, 1, 168, and 336 hours post infusion

  • Area Under the Concentration (AUC) at Day 1 [ Time Frame: Day 1 (Cycle 1) ] [ Designated as safety issue: No ]
    Evaluated at Baseline, 1, 168, and 336 hours post infusion

  • Half-life (t 1/2)at Day 1 [ Time Frame: Day 1 (Cycle 1) ] [ Designated as safety issue: No ]
    Evaluated at Baseline, 1, 168, and 336 hours post infusion

  • Clearance (CL) at Day 1 [ Time Frame: Day 1 (Cycle 1) ] [ Designated as safety issue: No ]
    Evaluated at Baseline, 1, 168, and 336 hours post infusion

  • Steady State Volume of distribution (Vss) at Day 1 [ Time Frame: Day 1 (Cycle 1) ] [ Designated as safety issue: No ]
    Evaluated at Baseline, 1, 168, and 336 hours post infusion

  • Maximum concentration (Cmax) at Day 1 [ Time Frame: Day 1 (Cycles 5, 9, 13, 17, and 21) ] [ Designated as safety issue: No ]
    Evaluated at Baseline and 1 hour post infusion

  • Area Under the Concentration (AUC) at Day 1 [ Time Frame: Day 1 (Cycles 5, 9, 13, 17, and 21) ] [ Designated as safety issue: No ]
    Evaluated at Baseline and 1 hour post infusion

  • Half-life (t 1/2) at Day 1 [ Time Frame: Day 1 (Cycles 5, 9, 13, 17, and 21) ] [ Designated as safety issue: No ]
    Evaluated at Baseline and 1 hour post infusion

  • Clearance (CL) at Day 1 [ Time Frame: Day 1 (Cycles 5, 9, 13, 17, and 21) ] [ Designated as safety issue: No ]
    Evaluated at Baseline and 1 hour post infusion

  • Steady State Volume of distribution (Vss) at Day 1 [ Time Frame: Day 1 (Cycles 5, 9, 13, 17, and 21) ] [ Designated as safety issue: No ]
    Evaluated at Baseline and 1 hour post infusion

  • Serum Anti-IMC-1121B (Immunogenicity) at Day 1 [ Time Frame: Day 1 (Cycles 1, 5, 9, and 30-day followup) ] [ Designated as safety issue: No ]
    Serum Anti-IMC-1121B evaluated prior to infusion


Enrollment: 48
Study Start Date: April 2009
Study Completion Date: August 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1121B (ramucirumab) + mFOLFOX-6
This regimen will be repeated every 2-weeks until disease progression, unacceptable toxicity, or withdrawal.
Biological: IMC-1121B (ramucirumab)
8 mg/kg IMC-1121B infusions every 2 weeks
Other Name: ramucirumab
Drug: Oxaliplatin
85 mg/m² intravenous (I.V.) infusion over 2 hours on Day 1
Drug: Folinic acid
400 mg/m² I.V. infusion over 2 hours on Day 1
Drug: 5-FU
400 mg/m² I.V. bolus injection over 2-4 minutes, immediately following folinic acid infusion
Drug: 5-FU
2400 mg/m² I.V. continuous infusion over 46 hours immediately following bolus 5-FU on days 1 and 2

Detailed Description:

The purpose of this study is to evaluate the progression-free survival (PFS) in patients with metastatic colorectal cancer when treated with the monoclonal antibody IMC-1121B in combination with the modified FOLFOX-6 (folinic acid [FA] + fluorouracil [5-FU0 + oxaliplatin, mFOLFOX-6) chemotherapy regimen as first-line therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient must have histologically confirmed adenocarcinoma of the colon or rectum that is locally-advanced or metastatic and unresectable
  • The patient has at least one unidimensionally-measurable target lesion (≥ 2 cm with conventional techniques or ≥ 1 cm with spiral computed tomography [CT] scan or magnetic resonance imaging [MRI], as defined by Response Evaluation Criteria in Solid Tumors [RECIST]); target lesion(s) must not lie within an irradiated area. Patients with locally advanced rectal carcinoma who have undergone previous radiation must have documented evidence of disease progression in the pelvis in order to participate
  • The patient is age ≥ 18 years
  • The patient has a life expectancy of ≥ 6 months
  • The patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 at study entry
  • The patient has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥ 1500/μL, hemoglobin ≥ 10 g/dL, and platelets

    ≥ 100,000/μL

  • The patient has adequate hepatic function as defined by: total bilirubin

    ≤ 1.5 x upper limit of normal (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN [or 5.0 x ULN in the case of liver metastases], and serum albumin ≥ lower limit of normal institutional range (LLN) or (if < LLN) within 10% of the LLN

  • The patient has adequate renal function as defined by a serum creatinine

    ≤ 1.5 x ULN, or creatinine clearance (measured via 24-hour urine collection)

    ≥ 60 mL/min

  • The patient's urinary protein ≤ 1+ on dipstick or routine urinalysis ([UA]; if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study)
  • The patient must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT)≤ 5 seconds above the ULN. Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight (LMW) heparin and if on warfarin, must have an INR between 2 and 3 and no active bleeding or pathological condition present that carries a high risk of bleeding (eg, tumor involving major vessels or known varices)
  • The patient has resolution to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3 (NCI-CTCAE v 3.0) of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy which must have resolved to Grade 0
  • The patient agrees to use adequate contraception during the study period and for 8 weeks after the last dose of study treatment
  • The patient has provided signed informed consent

Exclusion Criteria:

  • The patient has received prior systemic chemotherapy for locally-advanced unresectable or metastatic CRC. Prior adjuvant chemotherapy is allowed if disease progression has been documented > 6 months after the end of the last cycle of adjuvant chemotherapy or > 12 months after the end of the last cycle of adjuvant oxaliplatin-containing regimens
  • The patient has documented and/or symptomatic brain or leptomeningeal metastases
  • The patient has participated in clinical studies of non-approved experimental agents or procedures within 12 weeks of study entry
  • The patient has received previous therapy with monoclonal antibodies
  • The patient has received previous therapy with any agent that targets VEGF or VEGFR-2 (including multi-targeted tyrosine kinase inhibitors)
  • The patient has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator
  • The patient is on chronic non-topical corticosteroid treatment for > 6 months at doses > 10 mg/day of prednisolone or equivalent before study entry, which in the opinion of the investigator could compromise the patient or the study
  • The patient has a known dihydropyrimidine dehydrogenase (DPD) deficiency
  • The patient has a known allergy to any of the treatment components
  • The patient has an acute or subacute intestinal obstruction
  • The patient has uncontrolled or poorly controlled hypertension on a standard regimen of anti-hypertensive therapy
  • The patient has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm. A patient with previous history of malignancy is eligible, provided that he/she has been disease free for > 3 years
  • The patient, if female, is pregnant
  • Has had prior autologous or allogeneic organ or tissue transplantation
  • Has interstitial pneumonia or interstitial fibrosis of the lung, which in the opinion of the investigator could compromise the patient or the study
  • Has pleural effusion or ascites that causes > Grade 1 dyspnea
  • Has psychological, familial, sociological, or geographical conditions which do not permit adequate study follow-up, compliance with the protocol, or signature of Informed Consent
  • Has undergone major surgery within 28 days prior to the first dose of study medication, or subcutaneous venous access device placement within 7 days prior to the first dose of study medication
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00862784

Locations
Canada, Ontario
ImClone Investigational Site
Ottawa, Ontario, Canada, K1H 8L6
ImClone Investigational Site
Toronto, Ontario, Canada, M5G-2M9
Canada, Quebec
ImClone Investigational Site
Montreal, Quebec, Canada, H2L 4M1
Spain
ImClone Investigational Site
Barcelona, Spain
ImClone Investigational Site
Santander, Spain
ImClone Investigational Site
Seville, Spain
ImClone Investigational Site
Valencia, Spain
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: NCT00862784     History of Changes
Other Study ID Numbers: 13897, 2008-004936-19, CP12-0709, I4T-IE-JVBH
Study First Received: March 16, 2009
Last Updated: August 14, 2013
Health Authority: Canada: Health Canada
Spain: Spanish Agency of Medicines

Keywords provided by Eli Lilly and Company:
Colorectal carcinoma
CRC
Colon Cancer

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Leucovorin
Folic Acid
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on April 17, 2014