Overview

This trial is active, not recruiting.

Condition metastatic colorectal cancer
Treatments cetuximab + oxaliplatin + 5fu/fa, oxaliplatin + 5fu/fa
Phase phase 3
Sponsor Merck KGaA
Start date August 2010
End date January 2016
Trial size 503 participants
Trial identifier NCT01228734, EMR62202-057

Summary

The purpose of this study is 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
All eligible participants will receive the cetuximab in combination with FOLFOX4 regimen chemotherapy.
cetuximab + oxaliplatin + 5fu/fa Erbitux
Cetuximab will always be administered first, followed by oxaliplatin (85mg/m2, infused over 120 minutes) at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin folinic acid (FA) will be administered (at a dose of 200 mg/m2, infused over 120 minutes, on day 1 and day 2, every two weeks) and then 5-fluorouracil (5-FU) (as a bolus of 400 mg/m2/day IV over 2-4 minutes followed by 600 mg/m2/day infused over 22-hour, on day 1 and day 2, every two weeks). All subjects will receive treatment until the occurrence of progressive disease (PD) or unacceptable toxicity to cetuximab.
(Other)
All eligible participants will receive the FOLFOX4 regimen chemotherapy.
oxaliplatin + 5fu/fa
Oxaliplatin (85mg/m2, infused over 120 minutes) will always be administered first or simultaneously with oxaliplatin FA will be administered (at a dose of 200 mg/m2, infused over 120 minutes, on day 1 and day 2, every two weeks) and then 5-FU (as a bolus of 400 mg/m2/day IV over 2-4 minutes followed by 600 mg/m2/day infused over 22-hour, on day 1 and day 2, every two weeks). All subjects will receive treatment until the occurrence of progressive disease (PD) or unacceptable toxicity.

Primary Outcomes

Measure
Progression free survival (PFS)
time frame: Time from randomization to disease progression, death or last tumor assessment, reported between day of first patient randomised, Sep 2010, until cut-off date expected Dec 2015

Secondary Outcomes

Measure
Overall survival time
time frame: Time from randomization to death or last date known to be alive, reported between day of first patient randomised, Sep 2010, until cut-off date expected Dec 2015
Best overall response rate
time frame: Evaluations were performed every 8 weeks until progression, reported between day of first patient randomised, Sep 2010, until cut-off date expected Dec 2015
Time to treatment failure
time frame: Time from randomization to treatment failure or last tumor assessment, reported between day of first patient randomised, Sep 2010, until cut-off date expected Dec 2015
Rate of curative surgery for liver metastases
time frame: Time from randomization until end of treatment, reported between day of first patient randomised, Sep 2010, until cut-off date expected Dec 2015

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Signed written informed consent (first and second) - Chinese with Chinese citizenship - Male or female subjects ≥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

Additional Information

Official title An Open-label, Randomized, Controlled, Multicenter Phase III Trial to Compare Cetuximab in Combination With FOLFOX-4 Versus FOLFOX-4 Alone in the First Line Treatment of Metastatic Colorectal Cancer in Chinese Subjects With RAS Wild-type Status
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Merck KGaA.