A Study of IMC-1121B (Ramucirumab) in Colorectal Cancer

NCT ID: NCT00862784

Last Updated: 2014-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2011-08-31

Brief Summary

The purpose of this study is to test how long participants with colorectal cancer live without progressive disease when being treated with IMC-1121B (ramucirumab) and the modified FOLFOX-6 chemotherapy.

Detailed Description

The purpose of this study is to evaluate the progression-free survival (PFS) in participants with metastatic colorectal cancer when treated with the monoclonal antibody IMC-1121B (ramucirumab) in combination with the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] chemotherapy regimen as first-line therapy.

Conditions

Colorectal Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IMC-1121B (ramucirumab) + mFOLFOX-6

This regimen will be repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.

Group Type: EXPERIMENTAL

IMC-1121B (ramucirumab)

Intervention Type: BIOLOGICAL

8 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) infusions every 2 weeks

Oxaliplatin

Intervention Type: DRUG

85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1

Folinic acid

Intervention Type: DRUG

400 mg/m² intravenous infusion over 2 hours on Day 1

5-FU

Intervention Type: DRUG

400 mg/m² intravenous bolus injection over 2-4 minutes, immediately following folinic acid infusion

5-FU

Intervention Type: DRUG

2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU on Days 1 and 2

Interventions

IMC-1121B (ramucirumab)

8 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) infusions every 2 weeks

Intervention Type: BIOLOGICAL

Oxaliplatin

85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1

Intervention Type: DRUG

Folinic acid

400 mg/m² intravenous infusion over 2 hours on Day 1

Intervention Type: DRUG

5-FU

400 mg/m² intravenous bolus injection over 2-4 minutes, immediately following folinic acid infusion

Intervention Type: DRUG

5-FU

2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU on Days 1 and 2

Intervention Type: DRUG

Other Intervention Names

ramucirumab; LY3009806

Eligibility Criteria

Inclusion Criteria

• The participant must have histologically confirmed adenocarcinoma of the colon or rectum that is locally-advanced or metastatic and unresectable
• The participant has at least one unidimensionally-measurable target lesion [≥ 2 centimeters (cm) with conventional techniques or ≥ 1 cm with spiral computed tomography (CT) scan or magnetic resonance imaging (MRI), as defined by Response Evaluation Criteria in Solid Tumors (RECIST)]; target lesion(s) must not lie within an irradiated area. Participants with locally advanced rectal carcinoma who have undergone previous radiation must have documented evidence of disease progression in the pelvis in order to participate
• The participant is age ≥ 18 years
• The participant has a life expectancy of ≥ 6 months
• The participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 at study entry
• The participant has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥ 1500/microliter (μL), hemoglobin ≥ 10 grams/deciliter (g/dL), and platelets ≥ 100,000/μL
• The participant has adequate hepatic function as defined by: total bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN (or 5.0 x ULN in the case of liver metastases), and serum albumin ≥ lower limit of normal (LLN) institutional range or (if < LLN) within 10% of the LLN
• The participant has adequate renal function as defined by a serum creatinine ≤ 1.5 x ULN, or creatinine clearance (measured via 24-hour urine collection) ≥ 60 milliliters/minute (mL/min)
• The participant's urinary protein ≤ 1+ on dipstick or routine urinalysis [(UA); if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study]
• The participant must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight (LMW) heparin and if on warfarin, must have an INR between 2 and 3 and no active bleeding or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices)
• The participant has resolution to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3 (NCI-CTCAE v 3.0) of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy which must have resolved to Grade 0
• The participant agrees to use adequate contraception during the study period and for 8 weeks after the last dose of study treatment
• The participant has provided signed informed consent

Exclusion Criteria

• The participant has received prior systemic chemotherapy for locally-advanced unresectable or metastatic colorectal cancer (CRC). Prior adjuvant chemotherapy is allowed if disease progression has been documented > 6 months after the end of the last cycle of adjuvant chemotherapy or > 12 months after the end of the last cycle of adjuvant oxaliplatin-containing regimens
• The participant has documented and/or symptomatic brain or leptomeningeal metastases
• The participant has participated in clinical studies of non-approved experimental agents or procedures within 12 weeks of study entry
• The participant has received previous therapy with monoclonal antibodies
• The participant has received previous therapy with any agent that targets vascular endothelial growth factor (VEGF) or VEGF receptor-2 (VEGFR-2) (including multi-targeted tyrosine kinase inhibitors)
• The participant has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator
• The participant is on chronic non-topical corticosteroid treatment for > 6 months at doses > 10 mg/day of prednisolone or equivalent before study entry, which in the opinion of the investigator could compromise the participant or the study
• The participant has a known dihydropyrimidine dehydrogenase (DPD) deficiency
• The participant has a known allergy to any of the treatment components
• The participant has an acute or subacute intestinal obstruction
• The participant has uncontrolled or poorly controlled hypertension on a standard regimen of anti-hypertensive therapy
• The participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that he/she has been disease free for > 3 years
• The participant, if female, is pregnant
• Has had prior autologous or allogeneic organ or tissue transplantation
• Has interstitial pneumonia or interstitial fibrosis of the lung, which in the opinion of the investigator could compromise the participant or the study
• Has pleural effusion or ascites that causes > Grade 1 dyspnea
• Has psychological, familial, sociological, or geographical conditions which do not permit adequate study follow-up, compliance with the protocol, or signature of Informed Consent
• Has undergone major surgery within 28 days prior to the first dose of study medication, or subcutaneous venous access device placement within 7 days prior to the first dose of study medication

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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

Eli Lilly and Company

Locations

ImClone Investigational Site

Ottawa, Ontario, Canada

ImClone Investigational Site

Toronto, Ontario, Canada

ImClone Investigational Site

Montreal, Quebec, Canada

ImClone Investigational Site

Barcelona, , Spain

ImClone Investigational Site

Santander, , Spain

ImClone Investigational Site

Seville, , Spain

ImClone Investigational Site

Valencia, , Spain

Countries

Canada; Spain

Other Identifiers

2008-004936-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CP12-0709

Identifier Type: OTHER

Identifier Source: secondary_id

I4T-IE-JVBH

Identifier Type: OTHER

Identifier Source: secondary_id

13897

Identifier Type: -

Identifier Source: org_study_id