EMD 525797 in Combination With Cetuximab and Irinotecan in K-ras Wild Type Metastatic Colorectal Cancer

An Open-label, Randomized, Controlled, Multicenter, Phase I/II Trial Investigating 2 EMD 525797 Doses in Combination With Cetuximab and Irinotecan Versus Cetuximab and Irinotecan Alone, as Second-line Treatment for Subjects With K-ras Wild Type Metastatic Colorectal Cancer (mCRC)

The purpose of this study is to assess the safety and clinical activity of the experimental drug EMD 525797 (study drug), a monoclonal antibody targeting alfa integrins, in combination with irinotecan and cetuximab in K-ras wildtype metastatic colorectal cancer patients.

Inclusion Criteria:

Subjects with histologically confirmed kras wildtype (WT) colorectal carcinoma (CRC) with documented distant metastasis

• Prior oxaliplatin/fluoropyrimidine-containing regimen for the first-line treatment of metastatic disease
• Failed an oxaliplatin regimen for metastatic colorectal carcinoma (mCRC). Failure is defined as either progressive disease (PD) (clinical or radiologic) within 6 months of the last dose of any agent of an oxaliplatin-based regimen or intolerance to an oxaliplatin regimen. Intolerance to an oxaliplatin regimen is defined as discontinuation due to any of the following: severe allergic reaction, persistent severe neurotoxicity, or delayed recovery from toxicity preventing retreatment
• At least 1 radiographically documented measurable lesion in a previously non irradiated area according to Response Evaluation Criteria In Solid Tumors (RECIST, Version 1.0), i.e., this lesion must be adequately measurable in at least 1 dimension (longest diameter to be recorded) as greater than or equal to (>=) 2 centimeter (cm) by conventional techniques or >=1 cm by spiral computed tomography (CT) scan
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, or Karnofsky performance status (KPS) >= 80 percent (%)
• Absolute Neutrophil Count (ANC) >=1.5 x 10^9/Liter
• Platelets >=100 x 10^9/Liter
• Hemoglobin >=9 gram per deciliter (g/dL) (without transfusions)
• Bilirubin less than or equal to (<=) 1.5 x upper limit normal (ULN)
• Aspartate transaminase (AST) <=5 x ULN and alanine transaminase (ALT) <=5 x ULN
• Serum creatinine <=1.25 x ULN and/or creatinine clearance >=50 milliliter per minute (mL/min)
• International Nationalized Ratio (INR), and partial thromboplastin time (PTT) within normal limits
• Sodium and potassium within normal limits or <=10% above or below (supplementation permitted)

Exclusion Criteria:

• Previous treatment with any inhibitor of Epidermal Growth Factor Receptor (EGFR)
• Known brain metastasis and/or leptomeningeal disease
• Radiotherapy (except localized radiotherapy for pain relief), major surgery, or any investigational drug in the 30 days before the start of trial treatment entry; planned major surgery during the trial
• Concurrent chronic systemic immune or hormone therapy not indicated in this trial protocol (except for physiologic replacement; steroids up to 10 mg of prednisone equivalent or topical and inhaled steroids are allowed)
• Clinically relevant coronary artery disease (New York Heart Association [NYHA] functional angina classification III/IV), congestive heart failure (NYHA III/IV), clinically relevant cardiomyopathy, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia
• Uncontrolled hypertension defined as systolic blood pressure >=160 millimeter of mercury (mmHg) and/or diastolic blood pressure >=100 mmHg under resting conditions
• History of coagulation disorder associated with bleeding or recurrent thrombotic events
• History of recent peptic ulcer disease (endoscopically proven gastric, duodenal or esophageal ulcer) within 6 months of trial treatment start
• Chronic inflammatory bowel disease, or acute/chronic ileus
• Active infection (requiring i.v. antibiotics), including active tuberculosis, active or chronic Hepatitis B or C, or ongoing HIV infection