Phase II Study of Avastin + Erbitux + Irinotecan as 2nd Line Treatment of Colorectal Cancer

Study Overview
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Brief Summary
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This phase II study will evaluate the efficacy of the combination of two monoclonal antibodies (Avastin + Erbitux) with irinotecan, in patients with colorectal cancer progressed after 1st line treatment with FOLFIRI Avastin or XELIRI Avastin.

Detailed Description
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Treating patients with primary resistance to the most active multi-agent combination remains a challenging clinical problem. The reported data demonstrated that addition of ERBITUX may reverse IRINOTECAN resistance. Further data support the feasibility of the combination of two monoclonal antibodies (AVASTIN+ERBITUX) with IRINOTECAN with better responses compared to historical controls (ERBITUX±IRINOTECAN). As such, a phase II study was designed to evaluate the efficacy of the combination of AVASTIN plus ERBITUX plus IRINOTECAN as second line treatment in patients progressing while on treatment with FOLFIRI AVASTIN or XELIRI AVASTIN

Official Title
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Phase II Study of Avastin Plus Erbitux Plus Irinotecan as 2nd Line Treatment of Locally Advanced or Metastatic Colorectal Cancer in Patients Achieving Disease Progression as Best Response After 1st Line Treatment With FOLFIRI+Avastin or XELIRI+Avastin

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Irinotecan
* Drug: Avastin
* Drug: Erbitux


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed locally advanced or metastatic colorectal cancer. Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) ECOG performance status ≤ 2 Age 18 - 72 years Patients with de novo refractory disease (progression of disease as best response at 1st line therapy with FOLFOX/Avastin) Adequate liver (Bilirubin ≤ 1.5 UNL, SGOT/SGPT ≤ 4 UNL, ALP ≤ 2.5 UNL),renal (Creatinine ≤ 1.5 UNL) and bone marrow (ANC ≥ 1,500/mm3, PLT ≥100,000/mm3) function Patients must be able to understand the nature of this study Written informed consent Exclusion Criteria: History of serious cardiac disease (unstable angina, congestive heart failure, uncontrolled cardiac arrhythmias). History of myocardial infarction or stroke within 6 months. Clinically significant peripheral vascular disease. History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to Day 0. Presence of central nervous system or brain mets. Evidence of bleeding diathesis or coagulopathy. Patients with known hypersensitive reaction to cetuximab Blood pressure > 150/100 mmHg. Pregnant or lactating woman. Life expectancy < 3 months. Previous radiotherapy within the last 4 weeks or > 25% of bone marrow. Metastatic infiltration of the liver >50%. Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction or total colectomy. Active infection requiring antibiotics on Day 1. Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer. Psychiatric illness or social situation that would preclude study compliance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 72 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Irinotecan+Avastin+Erbitux | Drug: Irinotecan<br>* Irinotecan (IV) 150 mg/m2 on day 1 every two weeks until progression<br>* Other names: Campto;Drug: Avastin<br>* Avastin (IV) 10 mgr/Kgr on day 1 every 2 weeks until progression<br>* Other names: Bevacizumab;Drug: Erbitux<br>* Erbitux (IV)500 mg/m2 on day 1 every two weeks until progression<br>* Other names: Cetuximab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time To Progression |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate |  | Objective responses confirmed by CT or MRI (on 3rd and 6th cycle) | 
| Toxicity profile |  | Toxicity assessment on each chemotherapy cycle | 
| Quality of life, Symptoms improvement |  | Assessment every two cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic colorectal cancer, Second line, Irinotecan, Erbitux (Cetuximab), Avastin (Bevacizumab)