An Observational Study of Erbitux® in Patients With Metastatic Colorectal Cancer (mCRC) Refractory to Irinotecan-containing Treatment

Study Overview
=================
Brief Summary
-----------------
This is an observational, non-interventional, uncontrolled, multicentric safety study in subjects with epidermal growth factor receptor (EGFR)-expressing, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type mCRC. The study aims to collect safety data related to Erbitux treatment from a total of at least 400 mCRC subjects from about 35 institutions from the start of treatment with Erbitux until progressive disease, Erbitux-related intolerable toxicities, death, or withdrawal of Erbitux treatment (whichever occurs first).

Detailed Description
-----------------
Colorectal cancer is the fourth commonest form of cancer worldwide and remains a leading malignancy both in incidence and mortality. Erbitux is an immunoglobulin G1 monoclonal antibody that specifically blocks ligand binding to the EGFR with high affinity, thereby preventing downstream signal transduction and cellular responses. Erbitux enhances the effects of some common chemotherapy agents and radiotherapy and demonstrates minimal overlapping toxicities with these approaches. Erbitux in combination with other treatment modalities, has also shown efficacy in the treatment of a number of solid tumors, including mCRC, squamous cell carcinoma of the head and neck, and non-small cell lung cancer. Based on several studies conducted in the past, Erbitux has been approved for the treatment of subjects with EGFR-expressing, KRAS wild-type mCRC, as a single agent in subjects who have failed oxaliplatin-and irinotecan-based therapy and who are intolerant to irinotecan or in combination with chemotherapy. The most common Erbitux-related adverse events (AEs) are related to skin, infusion, and hypersensitivity reactions. Other side effects with Erbitux monotherapy include asthenia, dyspnoea, mucositis, nausea, pain, fever and headache. OBJECTIVES Primary objective: To obtain safety information on the use of Erbitux in subjects with EGFR-expressing, KRAS wild-type mCRC in terms of frequency and severity of AEs Secondary objective: To gather clinical efficacy information of the treatment The study will primarily collect safety data related to Erbitux treatment along with the clinical efficacy information from the start of treatment with Erbitux until progressive disease, Erbitux related intolerable toxicities, death, or withdrawal of Erbitux treatment whichever occurs first. All subjects will be enrolled in the order to visit the physician after making contract and each subject will be observed for a period of 4 months in average. Erbitux will be prescribed to mCRC subjects according to the approved national label as in routine clinical practice under the supervision of an investigator experienced in the use of antineoplastic medicinal products. Prior to the first infusion, subjects will receive pre-medication with an antihistamine and a corticosteroid. The initial dose of Erbitux is 400 mg/m2 body surface area and the subsequent weekly doses are 250 mg/m2 each administered intravenously (i.v.) via in-line filtration with an infusion pump, gravity drip, or a syringe pump. The recommended infusion period for the initial dose is 120 minutes and for the subsequent weekly doses is 60 minutes with the maximum infusion rate not exceeding 5 ml/min. The observational period of this study is defined as from the first infusion of Erbitux until 28 days after the last infusion of Erbitux in each subject, regardless the reason of discontinuation of Erbitux treatment.

Official Title
-----------------
Prospective, Multicenter, Observational Study on Erbitux® (Cetuximab) in Patients With EGFR-expressing, KRAS Wild-type Metastatic Colorectal Cancer

Conditions
-----------------
Colorectal Neoplasm

Intervention / Treatment
-----------------
* Drug: Cetuximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who are eligible for Erbitux treatment according to the indication in the national label of Erbitux (i.e. in EGFR expressing, KRAS wild-type metastatic colorectal adenocarcinoma). Subjects who have failed oxaliplatin and irinotecan-based therapy and who are intolerant to irinotecan in mCRC. Subjects who have signed the informed consent form Exclusion Criteria: Subjects who do not fall under the approved indications according to the national label of Erbitux.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cetuximab|In subjects with mCRC, cetuximab will be used in combination with chemotherapy or as a single agent according to the approved national label as in routine clinical practice. The initial dose of Erbitux is 400 mg/m2 body surface area and the subsequent weekly doses are 250 mg/m2 each administered i.v. via in-line filtration with an infusion pump, gravity drip, or a syringe pump. The recommended infusion period for the initial dose is 120 minutes and for the subsequent weekly doses is 60 minutes with the maximum infusion rate not exceeding 5 ml/min.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and toxicity of Erbitux treatment | Frequency and severity of all AEs and serious adverse events; Laboratory information (haematology, clinical chemistry, EGFR test and KRAS test). | 120 minutes and for the subsequent weekly doses is 60 minutes. Before, during and at the end of Erbitux treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy of Erbitux treatment | The following data will be collected: Best tumor response with Erbitux treatment Time to progression of tumor with Erbitux treatment Duration of response with Erbitux treatment | 120 minutes and for the subsequent weekly doses is 60 minutes From the start of treatment with Erbitux until progressive disease, Erbitux related intolerable toxicities, death, or withdrawal of Erbitux treatment whichever occurs first | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Colorectal cancer, Metastasis, Cetuximab, Erbitux, Epidermal growth factor receptor