Study Evaluating the Safety and Efficacy of FOLFIRI Plus Cetuximab or FOLFOX Plus Cetuximab as First-line Therapy in Subjects With KRAS Wild-type Metastatic Colorectal Cancer (APEC-Study)

Study Overview
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Brief Summary
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This is an open-label, non-randomized, multicenter Phase II study evaluating folinic acid + fluorouracil + irinotecan (FOLFIRI) plus cetuximab (Erbitux) or folinic acid + fluorouracil + oxaliplatin (FOLFOX) plus cetuximab as first-line therapy of patients with KRAS wild-type metastatic colorectal cancer. Only subjects with k-ras oncogene (KRAS) wild-type tumors are eligible. Efficacy will be assessed every 8 weeks. Treatment will be continued until progressive disease or unacceptable adverse events occur. After the end of study treatment, information on further anticancer treatment and survival will be collected every 3 months.

Official Title
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An Asia Pacific Non-randomized, Open-label Phase II Study Evaluating the Safety and Efficacy of FOLFIRI Plus Cetuximab (Erbitux) or FOLFOX Plus Cetuximab as First-line Therapy in Subjects With KRAS Wild-type Metastatic Colorectal Cancer (APEC-Study)

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Cetuximab
* Drug: FOLFIRI
* Drug: FOLFOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Inpatient or outpatient subjects, 18 years of age Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum Metastatic disease (M1) Life expectancy of at least 12 weeks Presence of at least 1 measurable index lesion (not lie in an irradiated area) by computed tomography (CT) scan or magnetic resonance imaging (MRI) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry Effective contraception for both male and female subjects if the risk of conception exists White blood cell count greater than or equal to (>=) 3,000 per cubic millimeter (/mm^3) with neutrophils >=1,500/mm3, platelet count >=100,000/mm3, hemoglobin >=5.6 millimole per liter (mmol/L) (9 gram per deciliter [g/dL]) Total bilirubin less than or equal to (<=) 1.5 x upper reference range Aspartate aminotransferase (AST) <=2.5 x upper reference range, or <=5 x upper reference range in case of liver metastasis Serum creatinine <=1.5 x upper reference range Recovery from relevant toxicity to previous treatment before study entry KRAS wild-type status of tumor tissue Exclusion Criteria: Previous chemotherapy for colorectal cancer except adjuvant treatment if terminated >6 months before the start of treatment in this study Radiotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before the start of treatment in this study Concurrent chronic systemic immune therapy, targeted therapy, anti-vascular endothelial growth factor (VEGF) therapy, or epidermal growth factor receptor (EGFR-) pathway targeting therapy not indicated in this study protocol Concurrent hormone therapy not indicated in this study protocol except for physiologic replacement or contraception Known hypersensitivity reaction to any of the components of study treatments Pregnancy (absence to be confirmed by beta human choriongonadotrophin [beta-hCG] test) or lactation period Brain metastasis and/or leptomeningeal disease (known or suspected) Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease Peripheral neuropathy > grade 1 Previous malignancy other than colorectal cancer in the last 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix Known alcohol or drug abuse Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent Participation in another clinical study within the past 30 days Significant disease which, in the investigator's opinion, would exclude the patient from the study Legal incapacity or limited legal capacity KRAS mutated status of tumor tissue

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab plus FOLFIRI<br> | Drug: Cetuximab<br>* Cetuximab will be administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.<br>* Other names: Erbitux;Drug: FOLFIRI<br>* Irinotecan will be administered intravenously at a dose of 180 mg/m^2 along with folinic acid administration intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form) and 5-fluorouracil will be administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m^2 given biweekly until disease progression, death, or consent withdrawal.<br>|
| Experimental: Cetuximab plus FOLFOX<br> | Drug: Cetuximab<br>* Cetuximab will be administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.<br>* Other names: Erbitux;Drug: FOLFOX<br>* Oxaliplatin will be administered intravenously at a dose of 100 mg/m^2 along with folinic acid administration intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form) and 5-fluorouracil administration intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m^2 given biweekly until disease progression, death, or consent withdrawal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Best Overall Confirmed Response Rate (BORR) | Response rate was defined as the percentage of subjects with BORR (confirmed complete response [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. As per RECIST v 1.0 criteria for target lesions and assessed by magnetic resonance imaging (MRI): CR = disappearance of all target lesions; PR = at least 30 percent (%) decrease in the sum of the longest diameter of target lesions. Response rate will be assessed every 8 weeks. | From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited until data cut-off date (31 May 2012) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) Time | PFS time was defined as the time from first administration of study drug until first observation of disease progression or death when death occurs within 90 days of the last tumor assessment or first study drug dose whichever occurred. | From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014) | 
| Overall Survival (OS) Time | OS time was defined as the time from first administration of study drug until date of death, assessed up to 5 years. OS time was censored if the subject was found to be alive on the last date of the assessment. | From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014) | 
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and TEAEs Leading to Death | An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. | From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mCRC