Clinical trial NCT01228734: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic colorectal cancer
RAS wild type
Cetuximab
First line treatment
First occurrence of metastatic colorectal cancer in Chinese subjects with RAS wildtype
status
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2010-10-26
Enrollment: 553
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Progression Free Survival (PFS) Time
timeFrame: Baseline up to 333 weeks
Secondary outcomes:
measure: Overall Survival (OS) Time
timeFrame: Baseline up to 333 weeks
measure: Best Overall Response Rate (ORR)
timeFrame: Baseline up to 333 weeks
measure: Time to Treatment Failure (TTF)
timeFrame: Baseline up to 333 weeks
measure: Number of Subjects With Curative Surgery of Liver Metastases
timeFrame: Baseline up to 333 weeks
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fujian Province Cancer Hospital
state: Fujian
city: Fuzhou
country: China
facility: Fuzhou General Hospital
state: Fujian
city: Guangzhou
country: China
facility: First Hospital Affiliated to Guangzhou University of Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Harbin
country: China
facility: The Tumor Hospital of Harbin Medical University
state: Heilongjiang
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: First Affiliated Hospital of Jilin University
state: Jilin
city: Qingdao
country: China
facility: The Affiliated Hospital of Medical College Qingdao University
state: Shandong
city: Hangzhou
country: China
facility: The First Affiliated Hospital of College of Medicine, Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
state: Zhejiang
city: Beijing
country: China
facility: 307 Hospital of PLA
city: Beijing
country: China
facility: The General Hospital of the People's Liberation Army
city: Bengbu
country: China
facility: Affiliated Hospital of Bengbu Medical College
city: Changsha, Hunan
country: China
facility: The Xiangya 2nd Hospital of Central South University
city: Chongqing
country: China
facility: Southwest Hospital
city: KunMing, Yunnan
country: China
facility: Yunnan Provincial Tumor Hospital
city: Nanchang, Jiangxi
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Shanghai
country: China
facility: Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Shanghai First People's Hospital
city: Shanghai
country: China
facility: Fudan University Zhongshan Hospital
city: Shuzhou, Jiangsu
country: China
facility: The First Affiliated Hospital of Soochow University
city: Tianjin
country: China
facility: Tianjin People's Hospital
city: Xi'an
country: China
facility: Xijing Hospital the 4th Military Medical University of PLA
Study officials:
affiliation: Merck Serono Co., Ltd., Beijing, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Wang H, Huang L, Gao P, Zhu Z, Ye W, Ding H, Fang L. Cost-effectiveness analysis of cetuximab combined with chemotherapy as a first-line treatment for patients with RAS wild-type metastatic colorectal cancer based on the TAILOR trial. BMJ Open. 2020 Feb 12;10(2):e030738. doi: 10.1136/bmjopen-2019-030738.
citation: Bai L, Zhang P, Zhou K, Liao W, Li Q. Cost-Effectiveness Analysis of First-Line Cetuximab Plus Leucovorin, Fluorouracil, and Oxaliplatin (FOLFOX-4) versus FOLFOX-4 in Patients with RAS Wild-Type Metastatic Colorectal Cancer. Cancer Manag Res. 2019 Dec 12;11:10419-10426. doi: 10.2147/CMAR.S219318. eCollection 2019.
citation: Qin S, Li J, Wang L, Xu J, Cheng Y, Bai Y, Li W, Xu N, Lin LZ, Wu Q, Li Y, Yang J, Pan H, Ouyang X, Qiu W, Wu K, Xiong J, Dai G, Liang H, Hu C, Zhang J, Tao M, Yao Q, Wang J, Chen J, Eggleton SP, Liu T. Efficacy and Tolerability of First-Line Cetuximab Plus Leucovorin, Fluorouracil, and Oxaliplatin (FOLFOX-4) Versus FOLFOX-4 in Patients With RAS Wild-Type Metastatic Colorectal Cancer: The Open-Label, Randomized, Phase III TAILOR Trial. J Clin Oncol. 2018 Oct 20;36(30):3031-3039. doi: 10.1200/JCO.2018.78.3183. Epub 2018 Sep 10.