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)

NCT ID: NCT00778830

Last Updated: 2015-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 289 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2014-04-30

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuximab plus FOLFIRI

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

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.

FOLFIRI

Intervention Type: DRUG

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.

Cetuximab plus FOLFOX

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

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.

FOLFOX

Intervention Type: DRUG

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.

Interventions

Cetuximab

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.

Intervention Type: DRUG

FOLFIRI

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.

Intervention Type: DRUG

FOLFOX

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.

Intervention Type: DRUG

Other Intervention Names

Erbitux

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Pte. Ltd., Singapore

INDUSTRY

Sponsor Role: collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck Pte. Ltd., Singapore

Locations

Research Site

Singapore, , Singapore

Countries

Singapore

Other Identifiers

EMR 62202-505

Identifier Type: -

Identifier Source: org_study_id