A Phase I/II Study of IXO With Bevacizumab in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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Triplets of irinotecan, oxaliplatin and infusional 5-fluorouracil(FU)/leucovorin (LV) are associated with high response rates and long survival as first-line treatment for metastatic colorectal cancer (mCRC). The oral fluoropyrimidine, capecitabine, is better tolerated and shows better response rates than 5-FU/LV in metastatic colorectal cancer. A phase I dose-escalation study established dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase II doses (RPIID) of irinotecan, oxaliplatin and capecitabine. This phase I /II study is to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), phase II recommended dose (RD) of IXO and bevacizumab combination and safety at the RD in an expanded cohort.

Official Title
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A Phase I/II Clinical Trial of Combination of Irinotecan, Xeloda and Oxaliplatin (IXO) Regimen With Avastin (Bevacizumab) in Patients With Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: IXO regimen + bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented adenocarcinoma of the colon or rectum. Advanced and/or metastatic disease, incurable with standard therapy. Unresectable advanced and/or metastatic unidimensionally measurable disease (RECIST scale). Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 Age: over 18 years. Adequate haematological, renal and hepatic functions Patient consent must be obtained according to local REB requirements. Patients must be accessible for treatment and follow up. Exclusion Criteria: Previous or concurrent malignancies Pregnant or lactating women. Women of childbearing potential must have had a negative pregnancy test within 7 days prior to registration. Concurrent treatment with other experimental drugs or anticancer therapy. Previous chemotherapy for advanced and/or metastatic disease. Previous adjuvant therapy with irinotecan or oxaliplatin. Previous full dose curative pelvic radiation therapy. Patients with documented brain metastases. Serious illness or medical condition. Gilbert's disease Use of enzyme inducing anticonvulsants such as phenytoin, phenobarbital and carbamazepine

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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IXO regimen + bevacizumab<br>This is phase I/II safety and efficacy study. There is only one arm of Irinotecan, Xeloda and Oxaliplatin (IXO) regimen with Avastin (bevacizumab) | Drug: IXO regimen + bevacizumab<br>* Phase I study - identifies the safety of IXO with bevacizumab and recommended phase II dose Phase II study - assesses efficacy and safety of IXO with bevacizumab<br>* Other names: bevacizumab - Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Assess the MTD and RD for phase II of IXO and bevacizumab combination given every 3 weeks in 1st line patients with mCRC |  | 3-week cycle, continuous monitoring of AE | 
| Phase II: Using the RD established in phase I, assess efficacy of the IXO with bevacizumab combination as measured by progression-free survival |  | 3-week cycle, continuous monitoring of AE | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rates and duration of response |  | every 2 cycles - 6 weeks | 
| Overall survival |  | continuous | 
| Qualitative and quantitative toxicity |  | continuous |