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

NCT01228734 | Completed Phase 3 Results DMC

• 1 other identifier: EMR62202-057
• Study Type: interventional
• Target: 553
• Locations: 1 country
• Sites: 25

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.

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

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Time

  PFS was defined as the duration (in months) from randomization until the first progressive disease (PD) observation as assessed by the Independent Review Committee (IRC) according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.0, or death due to any cause when death occurred within 90 days of randomization or the last tumor assessment, whichever was later. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of the target lesions, taking as references the smallest sum LD since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.

  Baseline up to 333 weeks

Secondary Outcomes (4)

• Overall Survival (OS) Time

  Baseline up to 333 weeks

• Best Overall Response Rate (ORR)

  Baseline up to 333 weeks

• Time to Treatment Failure (TTF)

  Baseline up to 333 weeks

• Number of Subjects With Curative Surgery of Liver Metastases

  Baseline up to 333 weeks

Study Arms (2)

Cetuximab + FOLFOX-4

EXPERIMENTAL

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.

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

FOLFOX-4

ACTIVE COMPARATOR

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.

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

Interventions

Cetuximab 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.

Also known as: Erbitux, C225

Cetuximab + FOLFOX-4

Oxaliplatin 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.

Cetuximab + FOLFOX-4; FOLFOX-4

Folinic Acid 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.

Cetuximab + FOLFOX-4; FOLFOX-4

5Fluorouracil 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.

Cetuximab + FOLFOX-4; FOLFOX-4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (25)

Fujian Province Cancer Hospital

Fuzhou, Fujian, 350014, China

Location

Fuzhou General Hospital

Fuzhou, Fujian, 350025, China

Location

First Hospital Affiliated to Guangzhou University of Chinese Medicine

Guangzhou, Guangdong, 510405, China

Location

Nanfang Hospital

Guangzhou, Guangdong, 510515, China

Location

The Tumor Hospital of Harbin Medical University

Harbin, Heilongjiang, 150040, China

Location

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

Wuhan, Hubei, 430023, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130012, China

Location

First Affiliated Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

The Affiliated Hospital of Medical College Qingdao University

Qingdao, Shandong, 266003, China

Location

The First Affiliated Hospital of College of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310009, China

Location

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

Hangzhou, Zhejiang, 310016, China

Location

307 Hospital of PLA

Beijing, 100071, China

Location

The General Hospital of the People's Liberation Army

Beijing, 100853, China

Location

Affiliated Hospital of Bengbu Medical College

Bengbu, 233004, China

Location

The Xiangya 2nd Hospital of Central South University

Changsha, Hunan, 410011, China

Location

Southwest Hospital

Chongqing, 400038, China

Location

Yunnan Provincial Tumor Hospital

KunMing, Yunnan, 650118, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, 200025, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Shanghai First People's Hospital

Shanghai, 200080, China

Location

Fudan University Zhongshan Hospital

Shanghai, China

Location

The First Affiliated Hospital of Soochow University

Shuzhou, Jiangsu, 215006, China

Location

Tianjin People's Hospital

Tianjin, 30000, China

Location

Xijing Hospital the 4th Military Medical University of PLA

Xi'an, 710032, China

Location

Related Publications (3)

• 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.

  PMID: 32051297 DERIVED

• 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.

  PMID: 31849531 DERIVED

• 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.

  PMID: 30199311 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2010
• First Posted: October 26, 2010
• Study Start: September 9, 2010
• Primary Completion: January 25, 2016
• Study Completion: January 31, 2018
• Last Updated: January 28, 2020
• Results First Posted: March 6, 2017

Record last verified: 2020-01

Locations

CN (25)