Clinical trial NCT01286818: A Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Carcinoma
Keywords: Colon Cancer
Rectal Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-01-31
Enrollment: 6
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period
timeFrame: Day 1, Cycle 1 through Day 1, Cycle 3 (1 cycle=14 days)
measure: Number of Participants With Ramucirumab Drug-Related Adverse Events or Serious Adverse Events
timeFrame: Baseline to end of study (up to 49.3 weeks) plus 37 day follow-up
Secondary outcomes:
measure: Number of Participants With Serum Anti-IMC-1121B Antibodies (Immunogenicity)
timeFrame: Day 1 of Cycle 5 (Week 9), Cycle 6 (Week 11), Cycle 7 (Week 13), and Cycle 9 (Week 17) [(1 cycle=14 days)]
measure: Maximum Concentration (Cmax) of Ramucirumab
timeFrame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
measure: Area Under the Curve (AUC) of Ramucirumab
timeFrame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
measure: Half Life (t1/2) of Ramucirumab
timeFrame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
measure: Clearance (CL) of Ramucirumab
timeFrame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
measure: Steady State Volume of Distribution (Vss) of Ramucirumab
timeFrame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
measure: Best Overall Response [Anti-Tumor Activity of FOLFIRI Plus Ramucirumab (IMC-1121B)]
timeFrame: Every 8 weeks until PD (up to 49 weeks)
Other outcomes:
Locations:
city: Chiba
country: Japan
facility: ImClone Investigational Site
city: Osaka
country: Japan
facility: ImClone Investigational Site
city: Shizuoka
country: Japan
facility: ImClone Investigational Site
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: