- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01634555
A Study to Assess the Pharmacokinetics of Ramucirumab (IMC-1121B) in Combination With FOLFIRI
February 3, 2019 updated by: Eli Lilly and Company
A Study to Evaluate the Potential of Concomitant Ramucirumab to Affect the Pharmacokinetics of Irinotecan and Its Metabolite SN-38 When Coadministered With Folinic Acid and 5 Fluorouracil in Patients With Advanced Malignant Solid Tumors
The purpose of this study is to assess the effect of concomitant ramucirumab (IMC-1121B) on the pharmacokinetics of irinotecan and its metabolite SN-38 when coadministered with folinic acid and 5-fluorouracil, in participants with advanced malignant solid tumors resistant to standard therapy or for which no standard therapy is available.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
29
Phase
- Phase 2
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
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Michigan
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Detroit, Michigan, United States, 48202
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
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Nevada
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Las Vegas, Nevada, United States, 89169
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
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Ohio
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Cleveland, Ohio, United States, 44195
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19111
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
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Pittsburgh, Pennsylvania, United States, 15213
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
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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
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Has histologic or cytologic documentation of a malignant solid tumor
- Has an advanced solid tumor that is resistant to standard therapy or for which no standard therapy is available
- Has resolution to Grade ≤1, per the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v. 4.0), of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Has adequate hematologic, coagulation, and hepatic function
- Has serum creatinine ≤ 1.5 x upper limit of normal (ULN)
- Urinary protein is <2+ on dipstick or routine urinalysis (UA) at study entry
- Women with childbearing potential must have a negative serum or urine pregnancy test
- Eligible participants of reproductive potential (both sexes) agree to use adequate method of contraception during the study period and for 12 weeks after the last dose of study medication
Exclusion Criteria:
- Has received a therapeutic monoclonal antibody within the last 42 days
- Has received cytotoxic chemotherapy within the last 21 days
- Has received radiotherapy within the last 14 days
- Are currently enrolled in, or discontinued within the last 14 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
- Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the last 3 months
- Has an uncontrolled illness, including, but not limited to uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders
- Has experienced any arterial thromboembolic event within the last 6 months
- Has known leptomeningeal disease or brain metastases or uncontrolled spinal cord compression
- Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
- Has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
- Has received a prior organ or transplantation
- Has undergone major surgery within the last 28 days
- Has had a serious nonhealing wound, ulcer, or bone fracture within the last 28 days
- Has an elective or planned major surgery to be performed during the course of the trial
- Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea
- Has experienced a Grade 3 or higher bleeding event within the last 3 months
- Has a known history or clinical evidence of Gilbert's Syndrome, or is known to have any of the following genotypes: uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1)*6/*6, UGT1A1*28/*28, or UGT1A1*6/*28
- Has received clinically relevant inhibitors or inducers of cytochrome P (CYP) 450 CYP3A4/5 or CYP2C9 and/or isoenzymes within the last 3 weeks
- Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis and a history of hepatic encephalopathy, or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
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: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: ramucirumab (IMC-1121B) and FOLFIRI
Treatment is sequential, Ramucirumab (IMC-1121B) will be administered before FOLFIRI ((Irinotecan + Folinic acid + 5-Fluorouracil).
FOLFIRI will be administered each cycle and Ramucirumab (IMC-1121B) will be administered beginning from Cycle 2 (2-week cycle).
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Ramucirumab (IMC-1121B) 8 milligrams per kilogram (mg/kg), administered as an intravenous (IV) infusion on Day 1 of each 2-week cycle (except Cycle 1)
Other Names:
180 milligrams per square meter (mg/m²) administered IV on Day 1 of each cycle
400 mg/m² administered IV on Day 1 of each cycle
400 mg/m² bolus over 2 to 4 minutes administered IV on Day 1 of each cycle, followed by 2400 mg/m² administered IV over 46 to 48 hours on Days 1 and 2 of each cycle
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Irinotecan and Its Metabolite SN-38 From Time Zero to Infinity [AUC(0-∞)] in Cycle 1
Time Frame: Cycle 1: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion
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Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose.
Data presented are Geometric Least Squares (Geo LS) means.
Geo LS means were adjusted for cycle, participant and random error.
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Cycle 1: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion
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Pharmacokinetics: Dose-Normalized AUC(0-∞) of Irinotecan and Its Metabolite SN-38 in Cycle 2
Time Frame: Cycle 2: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion
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Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose.
Data presented are Geo LS means.
Geo LS means were adjusted for cycle, participant and random error.
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Cycle 2: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion
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Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Irinotecan and Its Metabolite SN-38 in Cycle 1
Time Frame: Cycle 1: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion
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Dose-normalized Cmax was calculated from Cmax divided by the dose.
Data presented are Geo LS means.
Geo LS means were adjusted for cycle, participant and random error.
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Cycle 1: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion
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Pharmacokinetics: Dose-Normalized Cmax of Irinotecan and Its Metabolite SN-38 in Cycle 2
Time Frame: Cycle 2: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion
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Dose-normalized Cmax was calculated from Cmax divided by the dose.
Data presented are Geo LS means.
Geo LS means were adjusted for cycle, participant and random error.
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Cycle 2: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics: Cmax of Ramucirumab (IMC-1121B)
Time Frame: Cycle 2: -2, -1, -0.5, 0, 2, 3, 4, 5, 8, 10, 25, 48, 72, 96, 168, 264, 336 hours post-ramucirumab (IMC-1121B) infusion
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Cycle 2: -2, -1, -0.5, 0, 2, 3, 4, 5, 8, 10, 25, 48, 72, 96, 168, 264, 336 hours post-ramucirumab (IMC-1121B) infusion
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Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA)
Time Frame: Up To 2 Years
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Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group.
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Up To 2 Years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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
October 1, 2012
Primary Completion (ACTUAL)
August 1, 2013
Study Completion (ACTUAL)
February 1, 2018
Study Registration Dates
First Submitted
July 3, 2012
First Submitted That Met QC Criteria
July 3, 2012
First Posted (ESTIMATE)
July 6, 2012
Study Record Updates
Last Update Posted (ACTUAL)
February 26, 2019
Last Update Submitted That Met QC Criteria
February 3, 2019
Last Verified
February 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Topoisomerase Inhibitors
- Micronutrients
- Vitamins
- Topoisomerase I Inhibitors
- Antidotes
- Vitamin B Complex
- Hematinics
- Fluorouracil
- Leucovorin
- Irinotecan
- Levoleucovorin
- Ramucirumab
- Folic Acid
Other Study ID Numbers
- 14433
- CP12-1033 (OTHER: ImClone Systems)
- I4T-IE-JVCB (OTHER: 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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