A Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B)
|ClinicalTrials.gov Identifier: NCT01286818|
Recruitment Status : Completed
First Posted : January 31, 2011
Results First Posted : October 6, 2014
Last Update Posted : October 6, 2014
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Carcinoma||Biological: Ramucirumab (IMC-1121B) Drug: Irinotecan Drug: levofolinate Drug: 5-Fluorouracil (5-FU)||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||February 2011|
|Actual Primary Completion Date :||February 2012|
|Actual Study Completion Date :||March 2012|
|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:Drug: Irinotecan
IV Infusion, 180 milligrams per square meter (mg/m²) every 2 weeksDrug: levofolinate
IV infusion, 200 mg/m² every 2 weeksDrug: 5-Fluorouracil (5-FU)
400 mg/m² bolus followed by a 2400 mg/m² continuous infusion, every 2 weeks
- 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.
- 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.
- 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)] ]
- 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.
- 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).
- 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%.
- 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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01286818
|ImClone Investigational Site|
|Chiba, Japan, 277-8577|
|ImClone Investigational Site|
|Osaka, Japan, 569-8686|
|ImClone Investigational Site|
|Shizuoka, Japan, 411-8777|
|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|