A Study of Avastin (Bevacizumab) in Combination With Xelox and Tarceva in Patients With Metastatic Colorectal Cancer.

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of a first-line regimen of Avastin and Xelox (Xeloda + Eloxatin) followed by Avastin and Tarceva, in patients with metastatic colorectal cancer. Patients will receive 6 x 21 day cycles of treatment with Avastin (7.5mg/kg iv on day 1), Xeloda (1000mg/m2 po twice daily on days 1 to 14) and Eloxatin (130mg/m2 iv on day 1). Patients free of disease progression will then continue with Avastin (7.5mg/kg iv once every 3 weeks) and Tarceva (150mg po daily). 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 Study of the Effect of First-line Treatment With Avastin+Xelox, Followed by Avastin+Tarceva, on Progression-free Survival in Patients With Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: bevacizumab [Avastin]
* Drug: eloxatin
* Drug: capecitabine [Xeloda]
* Drug: erlotinib [Tarceva]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; adenocarcinoma of colon or rectum, with metastatic disease; >=1 measurable lesion. Exclusion Criteria: previous treatment with Avastin or Tarceva; previous systemic treatment for advanced or metastatic disease; adjuvant treatment for non-metastatic disease in past 6 months.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: bevacizumab [Avastin]<br>* Intravenous repeating dose<br>Drug: eloxatin<br>* Intravenous repeating dose<br>Drug: capecitabine [Xeloda]<br>* Oral repeating dose<br>Drug: erlotinib [Tarceva]<br>* Oral repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Progression or Death | Disease progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) as a 20 percent (%) increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions. | Start of study to approximately 4 years | 
| Progression-Free Survival | Progression-free survival was defined as the time from the date of informed consent until the date when the participant had progression of disease or died from disease progression. Participants who received surgical treatment after treatment ended were censored at the time of surgery. Participants who left the study for reasons other than progression of the disease were censored on the date on which they received a later antitumor therapy (with the same or different drugs, radiotherapy, or surgery). | From study start up to approximately 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Objective Response (Complete Response [CR] or Partial Response [PR]) | Percentage of participants with objective response based assessment of CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than [<]10 millimeters [mm]) and no new lesions. PR was defined as greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. | From study start up to approximately 4 years | 
| Percentage of Participants Achieving Disease Control (CR, PR, or No Change [NC]) | Percent of participants with confirmed CR, PR, or NC. Per RECIST version (v)1.0: CR was defined as disappearance of all target and non-target lesions. PR was defined as ≥30% decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions. NC was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non-target lesions. | From study start up to approximately 4 years | 
| Percentage of Participants Who Died |  | From study start up to approximately 4 years | 
| Overall Survival (OS) | Overall survival was defined as the time from the date of informed consent to the date of death (regardless of the cause of death). There was no restriction; survival was calculated until the date of death, even if another line of treatment was received, or until the date censored (last contact with the participant even if drugs different from the study treatment schedule were received). For all participants, survival information was collected until the date of death, the last contact, or the last follow-up. | From study start up to approximately 4 years |