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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)

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ClinicalTrials.gov Identifier: NCT01228734
Recruitment Status : Completed
First Posted : October 26, 2010
Results First Posted : March 6, 2017
Last Update Posted : January 28, 2020
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Cetuximab Drug: Oxaliplatin Drug: Folinic Acid Drug: 5Fluorouracil Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 553 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : September 9, 2010
Actual Primary Completion Date : January 25, 2016
Actual Study Completion Date : January 31, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: 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.
Other Names:
  • Erbitux
  • C225

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.

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.

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.

Active Comparator: 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.
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.

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.

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.




Primary Outcome Measures :
  1. Progression Free Survival (PFS) Time [ Time Frame: Baseline up to 333 weeks ]
    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.


Secondary Outcome Measures :
  1. Overall Survival (OS) Time [ Time Frame: Baseline up to 333 weeks ]
    OS was defined as the time (in months) from randomization to death. For subjects who were still alive at the analysis data cut-off date or who lost to follow-up, survival was censored at the last recorded date that the subject was known to be alive.

  2. Best Overall Response Rate (ORR) [ Time Frame: Baseline up to 333 weeks ]
    The Best ORR was defined as the percentage of subjects having achieved complete response (CR) or partial response (PR) according to RECIST version 1.0 as determined by the IRC. CR: defined as disappearance of all target and all non-target lesions and no new lesions. PR: defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters, no progression of non-target lesions and no new lesions.

  3. Time to Treatment Failure (TTF) [ Time Frame: Baseline up to 333 weeks ]
    TTF was defined as time from randomization to date of the first occurrence of radiologically confirmed PD as determined by IRC, Clinical PD according to the Investigator's assessment (if radiological confirmation of PD by IRC was unavailable), 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 or randomization. Subjects without event were censored on the date of last tumor assessment.

  4. Number of Subjects With Curative Surgery of Liver Metastases [ Time Frame: Baseline up to 333 weeks ]
    The number of subjects who underwent liver metastatic surgery after start of treatment and the outcome of surgery with respect to residual tumor after surgery (R0, R1, R2, not evaluable) were summarized. In case of resection of more than one metastasis, the worst outcome of surgery defined the overall status of a subject. R0 = No residual tumor after resection (all lesions resected completely); R1 = Metastases not resected completely with microscopic residual lesions; and R2 = Metastases not resected completely with macroscopic residual lesions.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01228734


Locations
Show Show 25 study locations
Sponsors and Collaborators
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck Serono Co., Ltd., Beijing, an affiliate of Merck KGaA, Darmstadt, Germany

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT01228734    
Other Study ID Numbers: EMR62202-057
First Posted: October 26, 2010    Key Record Dates
Results First Posted: March 6, 2017
Last Update Posted: January 28, 2020
Last Verified: January 2020
Keywords provided by Merck KGaA, Darmstadt, Germany:
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:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Leucovorin
Folic Acid
Oxaliplatin
Fluorouracil
Cetuximab
Levoleucovorin
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients