A Study of IMC-1121B (Ramucirumab) 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: May 16, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to test how long participants with colorectal cancer live without progressive disease when being treated with IMC-1121B (ramucirumab) 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: First dose to measured progressive disease or death due to any cause up to 28.1 months ] [ Designated as safety issue: No ]
    PFS was defined as the time from date of first dose to the first observation of progression of disease (PD) or death due to any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions and/or unequivocal progression of non-target lesion and/or new lesion. For participants who had no PD or death or had started new therapeutic anticancer treatment, PFS was censored at their last radiographic tumor assessment.


Secondary Outcome Measures:
  • Percentage of Participants With Complete Response or Partial Response [Objective Response Rate (ORR)] [ Time Frame: First dose to date of objective progressive disease up to 23.8 months ] [ Designated as safety issue: No ]
    ORR is the percentage of participants with a confirmed complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion. ORR is calculated as a total number of participants with CR or PR from the start of study treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100.

  • Overall Survival (OS) [ Time Frame: First dose to death due to any cause up to 28.1 months ] [ Designated as safety issue: No ]
    OS was defined as the time from first dose to the date of death due to any cause. For participants who were alive or were lost to follow-up, OS was censored on the last date the participant was known to be alive.

  • Duration of Response [ Time Frame: Time of response to time of measured progressive disease up to 22.2 months ] [ Designated as safety issue: No ]
    The duration of response was defined as the time from first objective status assessment of complete response (CR) or partial response (PR) to the first time of progression or death as a result of any cause. CR or PR is classified by the investigators according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion.

  • Number of Participants With IMC-1121B (Ramucirumab)-Related Adverse Events (AEs) [ Time Frame: First dose to 25.2 months ] [ Designated as safety issue: Yes ]
    Data presented are the number of participants who experienced AEs of any grade and AEs of Grade ≥3 based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v 3.0), that were considered to be related to IMC-1121B (ramucirumab) by the investigators. A summary of serious AEs (SAEs) and all other non-serious AEs regardless of causality, is located in the Reported Adverse Events module.

  • Number of Participants With IMC-1121B (Ramucirumab)-Related Severe Adverse Events (SAEs) [ Time Frame: First dose to 25.2 months ] [ Designated as safety issue: Yes ]
    Data presented are the number of participants who experienced SAEs, adverse events (AEs) resulting in death and AEs leading to discontinuation of treatment, that were considered to be related to IMC-1121B (ramucirumab) by the investigators. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

  • Maximum Concentration (Cmax) at Day 1 of Cycle 1 [ Time Frame: Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1) ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic schedule, Cmax was not calculated.

  • Area Under the Concentration (AUC) at Day 1 of Cycle 1 [ Time Frame: Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1) ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic schedule, AUC was not calculated.

  • Half-Life (t1/2) at Day 1 of Cycle 1 [ Time Frame: Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1) ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic schedule, t1/2 was not calculated.

  • Clearance (CL) at Day 1 of Cycle 1 [ Time Frame: Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1) ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic schedule, CL was not calculated.

  • Steady State Volume of Distribution (Vss) at Day 1 of Cycle 1 [ Time Frame: Baseline, 1, 168, and 336 hours post infusion Day 1 (Cycle 1) ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic schedule, Vss was not calculated.

  • Maximum Concentration (Cmax) at Day 1 of Cycles 5, 9, 13, 17, and 21 [ Time Frame: Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21) ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic schedule, Cmax was not calculated.

  • Area Under the Concentration (AUC) at Day 1 of Cycles 5, 9, 13, 17, and 21 [ Time Frame: Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21) ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic schedule, AUC was not calculated.

  • Half-Life (t1/2) at Day 1 of Cycles 5, 9, 13, 17, and 21 [ Time Frame: Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21) ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic schedule, t1/2 was not calculated.

  • Clearance (CL) at Day 1 of Cycles 5, 9, 13, 17, and 21 [ Time Frame: Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21) ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic schedule, CL was not calculated.

  • Steady State Volume of Distribution (Vss) at Day 1 of Cycles 5, 9, 13, 17, and 21 [ Time Frame: Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21) ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic schedule, Vss was not calculated.

  • Serum Anti-IMC-1121B (Immunogenicity) at Day 1 [ Time Frame: Day 1 (Cycles 1, 5, 9, and 30-day follow-up) ] [ Designated as safety issue: No ]
    Data presented are the number of participants with treatment emergent anti-IMC-112B antibodies.


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: IMC-1121B (ramucirumab) + mFOLFOX-6
This regimen will be repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Biological: IMC-1121B (ramucirumab)
8 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) infusions every 2 weeks
Other Names:
  • ramucirumab
  • LY3009806
Drug: Oxaliplatin
85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1
Drug: Folinic acid
400 mg/m² intravenous infusion over 2 hours on Day 1
Drug: 5-FU
400 mg/m² intravenous bolus injection over 2-4 minutes, immediately following folinic acid infusion
Drug: 5-FU
2400 mg/m² intravenous 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 participants with metastatic colorectal cancer when treated with the monoclonal antibody IMC-1121B (ramucirumab) in combination with the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + 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 participant must have histologically confirmed adenocarcinoma of the colon or rectum that is locally-advanced or metastatic and unresectable
  • The participant has at least one unidimensionally-measurable target lesion [≥ 2 centimeters (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. Participants 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 participant is age ≥ 18 years
  • The participant has a life expectancy of ≥ 6 months
  • The participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 at study entry
  • The participant has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥ 1500/microliter (μL), hemoglobin ≥ 10 grams/deciliter (g/dL), and platelets ≥ 100,000/μL
  • The participant 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 (LLN) institutional range or (if < LLN) within 10% of the LLN
  • The participant has adequate renal function as defined by a serum creatinine ≤ 1.5 x ULN, or creatinine clearance (measured via 24-hour urine collection) ≥ 60 milliliters/minute (mL/min)
  • The participant'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 milligrams (mg) of protein in 24 hours to allow participation in the study]
  • The participant 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. Participants 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 (for example, tumor involving major vessels or known varices)
  • The participant 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 participant agrees to use adequate contraception during the study period and for 8 weeks after the last dose of study treatment
  • The participant has provided signed informed consent

Exclusion Criteria:

  • The participant has received prior systemic chemotherapy for locally-advanced unresectable or metastatic colorectal cancer (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 participant has documented and/or symptomatic brain or leptomeningeal metastases
  • The participant has participated in clinical studies of non-approved experimental agents or procedures within 12 weeks of study entry
  • The participant has received previous therapy with monoclonal antibodies
  • The participant has received previous therapy with any agent that targets vascular endothelial growth factor (VEGF) or VEGF receptor-2 (VEGFR-2) (including multi-targeted tyrosine kinase inhibitors)
  • The participant 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 participant 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 participant or the study
  • The participant has a known dihydropyrimidine dehydrogenase (DPD) deficiency
  • The participant has a known allergy to any of the treatment components
  • The participant has an acute or subacute intestinal obstruction
  • The participant has uncontrolled or poorly controlled hypertension on a standard regimen of anti-hypertensive therapy
  • The participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that he/she has been disease free for > 3 years
  • The participant, 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 participant 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
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: 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
Results First Received: May 16, 2014
Last Updated: May 16, 2014
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
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Rectal Diseases
Folic Acid
Levoleucovorin
Oxaliplatin
Antidotes
Antineoplastic Agents
Growth Substances
Hematinics
Hematologic Agents
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on October 30, 2014