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

NCT01286818 | Completed Phase 1 Results DMC

• 3 other identifiers: 14223CP12-102914T-IE-JVBY
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

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).

Conditions

Colorectal Carcinoma

Keywords

Colon Cancer; Rectal Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period

  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

  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 Outcomes (7)

• Number of Participants With Serum Anti-IMC-1121B Antibodies (Immunogenicity)

  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

  Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)

• Area Under the Curve (AUC) of Ramucirumab

  Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)

• Half Life (t1/2) of Ramucirumab

  Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)

• Clearance (CL) of Ramucirumab

  Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)

Study Arms (1)

FOLFIRI plus Ramucirumab (IMC-1121B)

EXPERIMENTAL

Biological: Ramucirumab (IMC-1121B); Drug: Irinotecan; Drug: levofolinate; Drug: 5-Fluorouracil (5-FU)

Interventions

Ramucirumab (IMC-1121B) BIOLOGICAL

Ramucirumab (IMC-1121B): Intravenous (IV) infusions, 8 milligrams per kilogram (mg/kg) every 2 weeks

Also known as: IMC-1121B, Ramucirumab, LY3009806

FOLFIRI plus Ramucirumab (IMC-1121B)

Irinotecan DRUG

IV Infusion, 180 milligrams per square meter (mg/m²) every 2 weeks

FOLFIRI plus Ramucirumab (IMC-1121B)

levofolinate DRUG

IV infusion, 200 mg/m² every 2 weeks

FOLFIRI plus Ramucirumab (IMC-1121B)

5-Fluorouracil (5-FU) DRUG

400 mg/m² bolus followed by a 2400 mg/m² continuous infusion, every 2 weeks

FOLFIRI plus Ramucirumab (IMC-1121B)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (3)

ImClone Investigational Site

Chiba, 277-8577, Japan

Location

ImClone Investigational Site

Osaka, 569-8686, Japan

Location

ImClone Investigational Site

Shizuoka, 411-8777, Japan

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Ramucirumab; Irinotecan; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2011
• First Posted: January 31, 2011
• Study Start: February 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: March 1, 2012
• Last Updated: October 6, 2014
• Results First Posted: October 6, 2014

Record last verified: 2014-10

Locations

JP (3)