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

• Status: Completed
• Trial end date: 2015-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck KGaA; Merck KGaA, Darmstadt, Germany
• Treatments: Camptothecin; Cetuximab; Irinotecan

Criteria

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