A Trial to Compare Oxaliplatin, Folinic Acid (FA) and 5-Fluorouracil (5FU) Combination Chemotherapy (FOLFOX-4) With or Without Cetuximab in the 1st Line Treatment of Metastatic Colorectal Cancer (mCRC) in Chinese Rat Sarcoma Viral Oncogene Homolog (

• Status: Completed
• Trial end date: 2018-01-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study was to assess whether the progression free survival (PFS) time with FOLFOX-4 plus cetuximab is longer than that with FOLFOX-4 alone as first-line treatment for mCRC in Chinese subjects with RAS wild-type tumors.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck KGaA; Merck KGaA, Darmstadt, Germany
• Treatments: Cetuximab; Fluorouracil; Folic Acid; Leucovorin; Levoleucovorin; Oxaliplatin

Criteria

Inclusion Criteria:

• Signed written informed consent (first and second)

• Chinese with Chinese citizenship

• Male or female subjects greater than or equal to (>=) 18 years of age

• Medically accepted effective contraception if procreative potential exists (applicable for both male and female subjects until at least 90 days after the last dose of trial treatment)

• Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum

• First occurrence of metastatic disease (not curatively resectable) RAS wild-type status in tumor tissue

• At least one measurable lesion by computer tomography (CT) or magnetic resonance imaging (MRI) according to RECIST (not in an irradiated area)

• Life expectancy of at least 12 weeks

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at trial entry

• White blood cell count >= 3 × 10x9/L with neutrophils >= 1.5 × 10x9/L, platelet count >= 100 × 10x9/L and hemoglobin >= 6.21 mmol/L (10 g/dL)

• Total bilirubin <= 1.5 × upper limit of reference range

• Aspartate transaminase (AST) and alanine transaminase (ALT) <= 2.5 × upper limit of reference range or <= 5 × upper reference range in subjects with liver metastasis

• Serum creatinine <= 1.5 × upper limit of reference range

• Recovery from relevant toxicity due to previous treatment before trial entry

Exclusion Criteria:

• Previous chemotherapy for CRC except adjuvant treatment if terminated > 9 months (oxaliplatin-based chemotherapy) or > 6 months (non-oxaliplatin-based chemotherapy) before the start of treatment in this trial

• Radiotherapy or surgery (excluding prior diagnostic biopsy) in the 30 days before trial treatment

• Previous treatment with monoclonal antibody therapy, vascular endothelial growth factor (VEGF) pathway-targeting therapy, epidermal growth factor receptor (EGFR) pathway-targeting therapy, or other signal transduction inhibitors

• History of organ allograft, autologous stem cell transplantation, or allogeneic stem cell transplantation

• Renal replacement therapy

• Intake of any investigational medication within 30 days before trial entry

• Concurrent chronic systemic immune therapy or hormone therapy except physiologic replacement

• Granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) within 3 weeks of trial entry (these growth factors may be used during the trial thereafter)

• Other non-permitted concomitant anticancer therapies

• Known brain metastasis and/or leptomeningeal disease. Subjects with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis

• Previous malignancy other than CRC in the last 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix

• Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 5 years, or left ventricular ejection fraction below the institutional range of normal on a baseline multiple gated acquisition scan or echocardiogram

• Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease

• Active clinically serious infections (> grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0), including active tuberculosis

• Known and declared history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C

• Peripheral neuropathy > grade 1

• Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such

• Uncontrolled diabetes mellitus, pulmonary fibrosis, acute pulmonary disorder, interstitial pneumonia, or liver failure

• Known hypersensitivity or allergic reactions against any of the components of the trial treatments

• Pregnancy (absence to be confirmed by serum β-human chorionic gonadotropin test) or breastfeeding

• Ongoing alcohol or drug abuse

• Presence of a medical or psychological condition that would not permit the subject to complete the trial or sign informed consent

• Participation in another clinical trial within the past 30 days

• Other significant disease that in the investigator's opinion should exclude the subject from the trial

• Legal incapacity or limited legal capacity