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

NCT ID: NCT01228734

Last Updated: 2020-01-28

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

553 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-09-09

Study Completion Date

2018-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cetuximab + FOLFOX-4

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.

Group Type EXPERIMENTAL

Cetuximab

Intervention Type DRUG

Cetuximab was administered every 7 days at 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 until progression of disease, withdrawal of consent, or unacceptable toxicity to cetuximab.

Oxaliplatin

Intervention Type DRUG

Oxaliplatin 85 mg/m\^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Folinic Acid

Intervention Type DRUG

FA 200 mg/m\^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

5Fluorouracil

Intervention Type DRUG

5-FU as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infusion over 22 hours on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

FOLFOX-4

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.

Group Type ACTIVE_COMPARATOR

Oxaliplatin

Intervention Type DRUG

Oxaliplatin 85 mg/m\^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Folinic Acid

Intervention Type DRUG

FA 200 mg/m\^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

5Fluorouracil

Intervention Type DRUG

5-FU as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infusion over 22 hours on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Interventions

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Cetuximab

Cetuximab was administered every 7 days at 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 until progression of disease, withdrawal of consent, or unacceptable toxicity to cetuximab.

Intervention Type DRUG

Oxaliplatin

Oxaliplatin 85 mg/m\^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Intervention Type DRUG

Folinic Acid

FA 200 mg/m\^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Intervention Type DRUG

5Fluorouracil

5-FU as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infusion over 22 hours on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Intervention Type DRUG

Other Intervention Names

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Erbitux C225

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

Merck Serono Co., Ltd., Beijing, an affiliate of Merck KGaA, Darmstadt, Germany

Locations

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Fujian Province Cancer Hospital

Fuzhou, Fujian, China

Site Status

Fuzhou General Hospital

Fuzhou, Fujian, China

Site Status

First Hospital Affiliated to Guangzhou University of Chinese Medicine

Guangzhou, Guangdong, China

Site Status

Nanfang Hospital

Guangzhou, Guangdong, China

Site Status

The Tumor Hospital of Harbin Medical University

Harbin, Heilongjiang, China

Site Status

Union Hospital of Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status

Jilin Cancer Hospital

Changchun, Jilin, China

Site Status

First Affiliated Hospital of Jilin University

Changchun, Jilin, China

Site Status

The Affiliated Hospital of Medical College Qingdao University

Qingdao, Shandong, China

Site Status

The First Affiliated Hospital of College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Site Status

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Site Status

307 Hospital of PLA

Beijing, , China

Site Status

The General Hospital of the People's Liberation Army

Beijing, , China

Site Status

Affiliated Hospital of Bengbu Medical College

Bengbu, , China

Site Status

The Xiangya 2nd Hospital of Central South University

Changsha, Hunan, , China

Site Status

Southwest Hospital

Chongqing, , China

Site Status

Yunnan Provincial Tumor Hospital

KunMing, Yunnan, , China

Site Status

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, , China

Site Status

Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, , China

Site Status

Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status

Shanghai First People's Hospital

Shanghai, , China

Site Status

Fudan University Zhongshan Hospital

Shanghai, , China

Site Status

The First Affiliated Hospital of Soochow University

Shuzhou, Jiangsu, , China

Site Status

Tianjin People's Hospital

Tianjin, , China

Site Status

Xijing Hospital the 4th Military Medical University of PLA

Xi'an, , China

Site Status

Countries

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China

References

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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.

Reference Type DERIVED
PMID: 32051297 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31849531 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30199311 (View on PubMed)

Other Identifiers

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EMR62202-057

Identifier Type: -

Identifier Source: org_study_id

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