OPAL Study: A Study of Avastin (Bevacizumab) in Combination With FOLFOXIRI in Patients With Previously Untreated Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This single arm study will assess progression-free survival, feasibility of use and safety of Avastin in combination with 5-FU/FA, oxaliplatin and irinotecan (FOLFOXIRI) as first line treatment in patients with metastatic colorectal cancer. Patients will receive up to 12 bi-weekly cycles of Avastin (5mg/kg iv) in combination with this standard neoadjuvant chemotherapy regimen followed by up to 40 bi-weekly cycles with Avastin plus 5-FU/FA. The anticipated time on study treatment is until disease progression, and the target sample size is <100 individuals.

Official Title
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An Open Label, Single-arm, Phase II Study to Evaluate the Efficacy and the Feasibility of Bevacizumab (Avastin) Based on a FOLFOXIRI Regimen Until Progression in Patients With Previously Untreated Metastatic Colorectal Carcinoma(OPAL-Study)

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: 5-FU
* Drug: bevacizumab [Avastin]
* Drug: irinotecan
* Drug: leucovorin
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-70 years of age; metastatic colorectal cancer scheduled for standard first line chemotherapy; at least 1 measurable lesion; ECOG performance score of 0 or 1. Exclusion Criteria: prior chemotherapy for metastatic colorectal cancer; prior (neo)adjuvant chemotherapy/radiotherapy of a non-metastatic malignancy completed within 6 months prior to study entry; concomitant malignancies other CRC; history or evidence of CNS disease unrelated to cancer.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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> | Drug: 5-FU<br>* 3200mg/m2 continuous iv infusions, day 1 every 2 weeks<br>Drug: bevacizumab [Avastin]<br>* 5mg/kg iv infusion, day 1 every 2 weeks<br>Drug: irinotecan<br>* 165mg/m2 iv infusion, day 1 every 2 weeks<br>Drug: leucovorin<br>* 200mg/m2 iv infusion, day 1 every 2 weeks<br>Drug: oxaliplatin<br>* 85mg/m2 iv infusion, day 1 every 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | assessed every 8 weeks up to week 102, 3-monthly during follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival; proportion of patients achieving R0 resectability; objective response rate (complete response [CR] and partial response [PR]); proportion of patients completing 12 cycles of chemotherapy. |  | assessed every 4 weeks up to week 102 and at the end of follow-up period | 
| Proportion of patients with NCI-CTC grade 3-5 adverse events; adverse events, laboratory parameters, ECOG performance status. |  | Throughout study, laboratory analyses every 2 weeks, ECOG assessment every 8 weeks |