Randomized Phase III Study of Folfiri+Avastin Versus Xeliri+Avastin as 1st Line Treatment of CRC

Study Overview
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Brief Summary
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This phase III study will compare two combinations of irinotecan, Folfiri versus Xeliri, with the addition of Avastin as 1st line treatment of colorectal cancer.

Detailed Description
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There is no data of comparison for Folfiri and Xeliri regimens. The reported data demonstrated that the addition of Avastin in the combination of irinotecan/bolus 5-FU/LV has significant improvement of overall survival. Further analysis of these results showed that patients receiving irinotecan in combination with Avastin, as 1st line treatment and oxaliplatin with Avastin, as second line treatment, have median overall survival 25, 1 months, which is the longest survival that has been reported.

Official Title
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A Randomized Phase III Study of Irinotecan Plus 5-fluorouracil Plus Leucovorin and Bevacizumab (FOLFIRI+Avastin) Versus Irinotecan Plus Capecitabine and Bevacizumab (XELIRI+Avastin) as 1st Line Treatment of Locally Advanced or Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Irinotecan
* Drug: 5-Fluorouracil
* Drug: Leucovorin
* Drug: Capecitabine
* Drug: Bevacizumab
* Drug: Bevacizumab
* Drug: Irinotecan


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 ECOG performance status ≤ 2 Age 18 - 72 years 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 with history of hemoptysis or with increased risk of thromboembolic events should be observed carefully due to administration of Avastin Patients must be able to understand the nature of this study Written informed consent Exclusion Criteria: Previous 1st line chemotherapy Adjuvant chemotherapy with Irinotecan regimen with relapse < 6 months after the completion Active infection History of serious cardiac disease (unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias) Previous radiotherapy within the last 4 weeks or > 25% of bone marrow Patients with unstable CNS metastases Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer Psychiatric illness or social situation that would preclude study compliance Pregnant or lactating women Patients > 65 years with history of arterial thromboembolic, myocardial infarction, unstable angina and pulmonary embolism

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>FOLFIRI/Avastin | Drug: Irinotecan<br>* Irinotecan 150mg/m2 IV on day 1 every 2 weeks for 10 cycles<br>* Other names: CPT-11;Drug: 5-Fluorouracil<br>* 5-Fluorouracil 400 mg/m2 infused over 10 min IV and 5-FU 600 mg/m2 infused over 22 hours IV, on Day 1 and 2 (De Grammont regimen), every 2 weeks for 10 cycles<br>* Other names: 5-FU;Drug: Leucovorin<br>* Leucovorin 200 mg/m2 infused over 2 hours IV, on day 1 and 2 every 2 weeks for 10 cycles<br>* Other names: LV;Drug: Bevacizumab<br>* Bevacizumab 5mg/kg IV on day 1 every 2 weeks for 10 cycles<br>* Other names: Avastin;|
| Experimental: 2<br>XELIRI/Avastin | Drug: Capecitabine<br>* Capecitabine 2000mg/m2 p.o. daily, for days 1-14, every 3 weeks for 6 cycles<br>* Other names: Xeloda;Drug: Bevacizumab<br>* Bevacizumab 7,5mg/kg IV on day 1 every 3 weeks for 6 cycles<br>* Other names: Avastin;Drug: Irinotecan<br>* Irinotecan 250mg/m2 IV on day 1 every 3 weeks for 6 cycles<br>* Other names: CPT-11;|

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) | 
| Overall Survival |  | Probability of 1-year survival (%) | 
| Toxicity profile |  | Toxicity assessment on each chemotherapy cycle | 
| Quality of life |  | Assessment every two cycles | 
| 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, Irinotecan, Capecitabine, Bevacizumab