A Study to Assess the Pharmacokinetics of Ramucirumab (IMC-1121B) in Combination With FOLFIRI

NCT01634555 | Completed Phase 2 Results

• 3 other identifiers: 14433CP12-1033I4T-IE-JVCB
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Solid Tumors

Keywords

Advanced Malignant Solid Tumors

Outcome Measures

Primary Outcomes (4)

• 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

  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.

  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

• Pharmacokinetics: Dose-Normalized AUC(0-∞) of Irinotecan and Its Metabolite SN-38 in Cycle 2

  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.

  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

• Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Irinotecan and Its Metabolite SN-38 in Cycle 1

  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.

  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

• Pharmacokinetics: Dose-Normalized Cmax of Irinotecan and Its Metabolite SN-38 in Cycle 2

  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.

  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

Secondary Outcomes (2)

• Pharmacokinetics: Cmax of Ramucirumab (IMC-1121B)

  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

• Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA)

  Up To 2 Years

Study Arms (1)

ramucirumab (IMC-1121B) and FOLFIRI

EXPERIMENTAL

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).

Biological: Ramucirumab (IMC-1121B); Drug: Irinotecan; Drug: Folinic acid; Drug: 5-Fluorouracil

Interventions

Ramucirumab (IMC-1121B) BIOLOGICAL

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)

Also known as: IMC-1121B, LY3009806

ramucirumab (IMC-1121B) and FOLFIRI

Irinotecan DRUG

180 milligrams per square meter (mg/m²) administered IV on Day 1 of each cycle

ramucirumab (IMC-1121B) and FOLFIRI

Folinic acid DRUG

400 mg/m² administered IV on Day 1 of each cycle

ramucirumab (IMC-1121B) and FOLFIRI

5-Fluorouracil DRUG

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

ramucirumab (IMC-1121B) and FOLFIRI

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (5)

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

Detroit, Michigan, 48202, United States

Location

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

Las Vegas, Nevada, 89169, United States

Location

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

Cleveland, Ohio, 44195, United States

Location

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

Philadelphia, Pennsylvania, 19111, United States

Location

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

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Interventions

Ramucirumab; Irinotecan; Leucovorin; Fluorouracil

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

clinicaltrials.gov@lilly.com

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2012
• First Posted: July 6, 2012
• Study Start: October 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: February 1, 2018
• Last Updated: February 26, 2019
• Results First Posted: July 14, 2014

Record last verified: 2018-02

Locations

US (5)