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 (RAS) Wild-type Patients (TAILOR)

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 3

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Folinic Acid; Drug: Oxaliplatin; Drug: Cetuximab; Drug: 5Fluorouracil

Study type: Interventional

Funder types: Industry

Identifiers

NCT01228734

EMR62202-057

Details and patient eligibility

About

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.

Enrollment: 553 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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553 participants in 2 patient groups

Cetuximab + FOLFOX-4

Experimental group

Description:

Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-fluorouracil (5-FU)/folinic acid (FA). Cetuximab was always administered every 7 days with an initial dose of 400 milligram per square meter (mg/m\^2) at 5 milligram per minute (mg/min) and 250 mg/m\^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m\^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m\^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.

Treatment:

Drug: Folinic Acid

Drug: 5Fluorouracil

Drug: Oxaliplatin

Drug: Cetuximab

FOLFOX-4

Active Comparator group

Description:

Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m\^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m\^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.

Treatment:

Drug: Folinic Acid

Drug: 5Fluorouracil

Drug: Oxaliplatin