ANGIOPREDICT. ICORG 12-16, V3

Study Overview
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Brief Summary
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Primary Objective: The primary objective is to validate previously identified predictive/prognostic genomic DNA and expression biomarkers of response to combination bvz treatments in K-ras mutant advanced CRC (a CRC) or metastatic CRC (mCRC). Secondary Objective: To test the efficacy of bvz in combination with FOLFOX in patients with newly diagnosed advanced or metastatic K-ras mutant CRC and To determine the progression free and overall survival of patients under first line FOLFOX + bvz in aCRC or mCRC.

Detailed Description
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Study Design: Type of Study: Exploratory, translational, multicenter and multinational Phase II study. Patient Population:All patients from the intent-to-treat population with aCRC or mCRC, (incurable with any conventional multimodality approach) and who fulfil all inclusion and exclusion criteria. Number of Patients: 224 Sample Type: Serial tissue and blood samples will be collected before (week 0), during (week 6, month 3 and 6) and at the end of treatment (month 12).

Official Title
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Exploratory Phase II Clinical Trial Comprising Biomarker Analysis of Oxaliplatin Plus Fluorouracil/Leucovorin (FOLFOX) in Combination With Bevacizumab (Bvz) in First Line Treatment of Metastatic Colorectal Cancer (CRC) Expressing Mutant K-ras - AC-ANGIOPREDICT

Conditions
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Advanced Colorectal Cancer

Intervention / Treatment
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* Other: Biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years of age. Patients diagnosed with recurrent or de novo, locally advanced (unresectable) or metastatic adenocarcinoma of the colon or rectum. Planned combination bevacizumab (bvz) treatment with either: leucovorin, fluorouracil and oxaliplatin (FOLFOX) capecitabine and oxaliplatin (XELOX) leucovorin, fluorouracil and irinotecan (FOLFIRI) capecitabine and irinotecan (XELIRI) Naive for bvz An evaluable site of disease ECOG Performance status 0, 1, or 2 Adequate renal function as shown by serum creatinine ≤ 1.5 x ULN or GFR ≥ 50ml/min Adequate hematopoietic function [white blood cell (WBC) count ≥ 3000/μl, absolute neutrophil count (ANC) ≥1500/μl, platelets ≥100 000/μl, haemoglobin level ≥ 9.0 g/dl] Adequate end organ function, defined as the following: total bilirubin < 1.5 x ULN, SGOT and SGPT < 3.0 x ULN (in case of liver metastases SGOT and SGPT < 5.0 x ULN) Ability to give signed informed consent prior to any screening procedures FFPE Tissue is available Exclusion Criteria: Patient has received any other investigational product within 28 days of first day of study drug dosing Patients having familial and/or hereditary CRC CRC associated with ulcerative colitis Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Intent-to-treat population with aCRC or mCRC<br>Advanced Colorectal Cancer with planned treatment with a aCRC or mCRC and who fulfil all inclusion and exclusion criteria | Other: Biomarker analysis<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of biomarkers | Identification of biomarkers, which are predictive for response and/or prolonged PFS to FOLFOX/bvz combination therapy in aCRC or mCRC patients. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validation of identified biomarkers | Validation of identified biomarkers with regard to response rate/failure to further treatment strategy, PFS, overall survival (OS) and toxicity. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rectal Cancer, Colorectal Cancer, Advanced Colorectal Cancer, Metastatic Colorectal Cancer, Locally Advanced Colorectal Cancer, Colon Cancer