A Study of IMC-1121B (Ramucirumab) in Colorectal Cancer
Condition: Colorectal Carcinoma
MeSH terms: Colorectal Neoplasms
Intervention: IMC-1121B (ramucirumab); Oxaliplatin; Folinic acid; 5-FU; 5-FU
Intervention description: 8 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) infusions every 2 weeks; 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; 400 mg/m² intravenous infusion over 2 hours on Day 1; 400 mg/m² intravenous bolus injection over 2-4 minutes, immediately following folinic acid infusion; 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU on Days 1 and 2
Intervention MeSH terms: Leucovorin; Folic Acid; Oxaliplatin; Fluorouracil; Ramucirumab; Antibodies, Monoclonal; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Colorectal carcinoma; CRC; Colon Cancer

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.
    

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