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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01228734
First received: September 9, 2010
Last updated: June 20, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Cetuximab + Oxaliplatin + 5FU/FA
Drug: Oxaliplatin + 5FU/FA
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    PFS is defined as duration from randomization until radiological progression (based on Response Evaluation Criteria In Solid Tumors (RECIST)) or death due to any cause. Only deaths within 90 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.

  • 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 ] [ Designated as safety issue: No ]
    The best overall response rate is defined as the proportion of subjects having achieved confirmed Complete Response + Partial Response as the best overall response according to radiological assessments (based on modified RECIST criteria).

  • 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 ] [ Designated as safety issue: No ]
    Time to treatment failure is defined as time from randomization to date of the first occurrence of; progression, discontinuation of treatment due to progression or adverse event, start of new anticancer therapy, withdrawal of consent, or death (within 90 days of last tumor assessment). Patients without event are censored on the date of last tumor assessment.

  • 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 ] [ Designated as safety issue: No ]

Enrollment: 481
Study Start Date: September 2010
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab plus FOLFOX4
All eligible participants will receive the cetuximab in combination with FOLFOX4 regimen chemotherapy.
Drug: Cetuximab + Oxaliplatin + 5FU/FA
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 Names:
  • Erbitux
  • C225
FOLFOX4
All eligible participants will receive the FOLFOX4 regimen chemotherapy.
Drug: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01228734

Locations
China, Fujian
Fujian Province Cancer Hospital
Fuzhou, Fujian, China, 350014
China, Guangdong
First Hospital Affiliated to Guangzhou University of Chinese Medicine
Guangzhou, Guangdong, China, 510405
China, Hubei
Union Hospital of Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, China, 430023
China, Jilin
Jilin Cancer Hospital
Changchun, Jilin, China, 130012
China, Zhejiang
The First Affiliated Hospital of College of Medicine, Zhejiang University
Hangzhou, Zhejiang, China, 310009
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, China, 310016
China
307 Hospital of PLA
Beijing, China, 100071
The General Hospital of the People's Liberation Army
Beijing, China, 100853
Affiliated Hospital of Bengbu Medical College
Bengbu, China, 233004
First Affiliated Hospital of Jilin University
Changchun, China
The Xiangya 2nd Hospital of Central South University
Changsha, Hunan, China
Southwest Hospital
Chongqing, China, 4000388
Fuzhou General Hospital
Fuzhou, China, 350025
The Tumor Hospital of Harbin Medical University
Harbin, China, 150040
Yunan Provincial Tumor Hospital
KunMing, Yuanani, China
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, China
The Affiliated Hospital of Medical College Qingdao University
Qingdao, China, 266003
Fudan University Zhongshan Hospital
Shanghai, China
Shanghai First People's Hospital
Shanghai, China, 200080
Fudan University Shanghai Cancer Center
Shanghai, China, 200032
Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, China, 200025
The First Affiliated Hospital of Soochow University
Shuzhou, Jiangsu, China
Tianjin People's Hospital
Tianjin, China
Xijing Hospital the 4th Military Medical University of PLA
Xi'an, China
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Medical Responsible Merck Serono Co., Ltd., Beijing, an affiliate of Merck KGaA, Darmstadt, Germany
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01228734     History of Changes
Other Study ID Numbers: EMR62202-057
Study First Received: September 9, 2010
Last Updated: June 20, 2014
Health Authority: China: Ministry of Health
China: Food and Drug Administration

Keywords provided by Merck KGaA:
Metastatic colorectal cancer
RAS wild type
Cetuximab
First line treatment
First occurrence of metastatic colorectal cancer in Chinese subjects with RAS wildtype
status

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Cetuximab
Leucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on August 27, 2014