A Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B)

October 3, 2014 updated by: Eli Lilly and Company

A Phase 1b Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B) Drug Product in Japanese Subjects With Metastatic Colorectal Carcinoma Progressive During or Following First-Line Combination Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine

The primary objective of this study is to investigate the safety and tolerability of the anti-vascular endothelial growth factor receptor-2 (anti-VEGFR-2) monoclonal antibody Ramucirumab (IMC-1121B) in combination with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) in Japanese participants with advanced colorectal carcinoma (CRC).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Chiba, Japan, 277-8577
        • ImClone Investigational Site
      • Osaka, Japan, 569-8686
        • ImClone Investigational Site
      • Shizuoka, Japan, 411-8777
        • ImClone Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participant is Japanese
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Has histologically or cytologically confirmed CRC
  • Has metastatic disease that is not amenable to potentially curative resection
  • Has received no more than 2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted)
  • Has received first-line combination therapy of bevacizumab, oxaliplatin, and a fluoropyrimidine for metastatic disease and has experienced disease progression during first-line therapy, or disease progression within 6 months after the last dose of first-line therapy, or discontinued part or all of first-line therapy due to toxicity and experienced disease progression within 6 months after the last dose of first-line therapy. Participants must have received a minimum of 2 doses of bevacizumab as part of a first-line regimen containing chemotherapy in order to enroll.
  • Has adequate hepatic, renal, hematologic, and coagulation function
  • The participant's urinary protein is ≤1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥2+, then a 24-hour urine must be collected and must demonstrate <1000 milligrams (mg) of protein in 24 hours to allow participation in the study

Exclusion Criteria:

  • Has received bevacizumab within 28 days prior to study registration
  • Has received chemotherapy within 21 days prior to study registration
  • Has received any previous systemic therapy (other than a combination of bevacizumab, oxaliplatin, and a fluoropyrimidine) for first-line treatment of metastatic CRC
  • The participant experienced any of the following during first-line therapy with a bevacizumab-containing regimen: an arterial thrombotic/thromboembolic event; Grade 4 hypertension; Grade 4 proteinuria; a Grade 3-4 bleeding event; or bowel perforation
  • Has received wide-field (full-dose pelvic) radiotherapy within 28 days prior to study registration
  • Has undergone major surgery within 28 days or subcutaneous venous access device placement within 7 days prior to study registration
  • Has elective or planned surgery to be conducted during the trial
  • Has a history of deep vein thrombosis or pulmonary embolism within the past 12 months
  • Has experienced any arterial thrombotic event within the past 12 months
  • Participant is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin, or similar agents
  • Participant is receiving chronic therapy with nonsteroidal anti-inflammatory agents [Aspirin up to 325 milligrams per day (mg/day) permitted]
  • Has a significant bleeding disorder or has had a significant (Grade 3 or higher) bleeding event within 3 months prior to registration date
  • Has a history of gastrointestinal perforation and/or fistulae within 6 months prior to registration date
  • Has symptomatic congestive heart failure, unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia
  • Has uncontrolled arterial hypertension despite standard medical management
  • Has a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to study registration
  • Has an acute/subacute bowel obstruction or history of clinically significant chronic diarrhea
  • Has a history of inflammatory bowel disease or Crohn's disease requiring medical intervention within 12 months prior to registration date
  • The participant has either peptic ulcer disease associated with a bleeding event or known active diverticulitis
  • Has an active infection requiring antibiotic, antifungal, or antiviral therapy
  • Has known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness
  • Has known leptomeningeal or brain metastases or uncontrolled spinal cord compression
  • Has a known history of Gilbert's Syndrome, or is known to have any of the following genotypes: uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)*6/*6; UGT1A1*28/*28 or UGT1A1*6/*28
  • Has previous or concurrent malignancy, except for basal or squamous cell skin cancer and/or in situ carcinoma, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: FOLFIRI plus Ramucirumab (IMC-1121B)
Biological: Ramucirumab (IMC-1121B)
Ramucirumab (IMC-1121B): Intravenous (IV) infusions, 8 milligrams per kilogram (mg/kg) every 2 weeks
Other Names:
  • LY3009806
  • IMC-1121B
  • Ramucirumab
Drug: Irinotecan
IV Infusion, 180 milligrams per square meter (mg/m²) every 2 weeks
Drug: levofolinate
IV infusion, 200 mg/m² every 2 weeks
Drug: 5-Fluorouracil (5-FU)
400 mg/m² bolus followed by a 2400 mg/m² continuous infusion, every 2 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period
Time Frame: Day 1, Cycle 1 through Day 1, Cycle 3 (1 cycle=14 days)
DLTs were adverse events (AEs) possibly related to study drug that met the National Cancer Institute's Common Terminology Criteria for AEs (NCI CTCAE, version 4.03): Grade 4 neutropenia ≥7 days or ≥Grade 3 with bacteremia or sepsis; Absolute neutrophil count <1.0x10^9/Liters with fever ≥38.3°Celsius requiring intravenous antibiotic therapy; Grade 4 thrombocytopenia or ≥Grade 3 with bleeding requiring platelet transfusion; ≥Grade 3 altered coagulation tests and no anticoagulation; ≥Grade 4 or uncontrolled hypertension; ≥Grade 3 non-hematologic toxicity (except non-clinically significant Grade 3 events like electrolyte abnormality, hypersensitivity, and arthralgia/myalgia); urine protein >3 grams/24 hours; study drug-related toxicity causing Cycle 3, Day 1 treatment delay until Day 44 or later. Grade 3 or Grade 4 infusion-related reaction (hypersensitivity) due to ramucirumab or FOLFIRI, not a DLT.
Day 1, Cycle 1 through Day 1, Cycle 3 (1 cycle=14 days)
Number of Participants With Ramucirumab Drug-Related Adverse Events or Serious Adverse Events
Time Frame: Baseline to end of study (up to 49.3 weeks) plus 37 day follow-up
Data are presented for the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade ≥3 TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered to be related to ramucirumab. Events related to Irinotecan, Levofolinate, and 5-fluorouracil (5-FU) were reported separately. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Baseline to end of study (up to 49.3 weeks) plus 37 day follow-up

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Serum Anti-IMC-1121B Antibodies (Immunogenicity)
Time Frame: Day 1 of Cycle 5 (Week 9), Cycle 6 (Week 11), Cycle 7 (Week 13), and Cycle 9 (Week 17) [(1 cycle=14 days)]
Day 1 of Cycle 5 (Week 9), Cycle 6 (Week 11), Cycle 7 (Week 13), and Cycle 9 (Week 17) [(1 cycle=14 days)]
Maximum Concentration (Cmax) of Ramucirumab
Time Frame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
The Cmax of ramucirumab in serum on Day 1, Cycle 1 and on Day 1, Cycle 5, which was also considered Cmax at steady state (Cmax,ss), is reported.
Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Area Under the Curve (AUC) of Ramucirumab
Time Frame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Reported for Day 1, Cycle 1 is AUC from time 0 extrapolated to infinity [AUC(0-inf)] and for Day 1, Cycle 5 is AUC over the dosing interval at steady state AUC(tau,ss).
Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Half Life (t1/2) of Ramucirumab
Time Frame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
t1/2 is the time required for the plasma/serum concentration to decrease 50%.
Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Clearance (CL) of Ramucirumab
Time Frame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
The total body CL of ramucirumab on Day 1, Cycle 1 and on Day 1, Cycle 5, which was also considered CL at steady state (CLss), is reported.
Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Steady State Volume of Distribution (Vss) of Ramucirumab
Time Frame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Vss is the theoretical volume in which the total amount of study drug would need to be uniformly distributed during steady state to produce the same concentration as it is in plasma/serum.
Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Best Overall Response [Anti-Tumor Activity of FOLFIRI Plus Ramucirumab (IMC-1121B)]
Time Frame: Every 8 weeks until PD (up to 49 weeks)
Best overall response evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR): disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Progressive Disease (PD): an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). In addition, the sum must have demonstrated an absolute increase of at least 5 mm (the appearance of 1 or more new lesions was considered progression). Stable Disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started.
Every 8 weeks until PD (up to 49 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eli Lilly and Company

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 25, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 28, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 31, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 6, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 3, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 14223
  • CP12-1029 (Other Identifier: ImClone Systems)
  • 14T-IE-JVBY (Other Identifier: Eli Lilly and Company)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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