Bevacizumab, Erlotinib, and Imatinib in the Treatment of Advanced Renal Cell Carcinoma

Study Overview
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Brief Summary
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This phase I/II trial will evaluate the bevacizumab/erlotinib combination with the addition of imatinib (Gleevec). The combined inhibition greatly enhances the anti-tumor effects. Although the safety of the bevacizumab/erlotinib/imatinib combination has not yet been demonstrated, the mild to moderate side effects of all of these agents are not predicted to cause prohibitive toxicity. A brief phase I portion will be included in this trial, to optimize doses of the 3 agents prior to proceeding with the phase II trial.

Detailed Description
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Upon determination of eligibility, patients will be receive: Bevacizumab + Erlotinib + Imatinib A brief phase I dose escalation study will be performed to define the imatinib dose that will be used.

Official Title
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A Phase I/II Trial of Bevacizumab (Avastin), Erlotinib (Tarceva), and Imatinib (Gleevec) in the Treatment of Patients With Advanced Renal Cell Carcinoma

Conditions
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Clear Cell Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Erlotinib
* Drug: Imatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be included in this study, you must meet the following criteria: Metastatic or unresectable clear cell renal carcinoma confirmed by biopsy Previous nephrectomy is required Maximum of 1 previous systemic regimen for metastatic disease. Able to perform activities of daily living with minimal assistance Measurable disease Adequate bone marrow, liver and kidney Written informed consent. Exclusion Criteria: Age < 18 years Treatment with more than 1 previous systemic regimen History of heart attack within 6 months Clinically significant cardiovascular disease Moderate to severe vascular disease. Active brain metastases. History or evidence by physical examination of brain tumor Seizures not controlled with standard medical therapy history of stroke or other serious disorders of the nervous system Clinical history of coughing or vomiting blood within the past 3 months. PEG tubes or G tubes Chronic therapy with NSAIDS or other platelet inhibitors Proteinuria Nonhealing wound, ulcer, or long bone fracture Clinical evidence or history of a bleeding disorder Requiring full dose anticoagulation with coumadin Receiving chronic steroid therapy Significant medical conditions. Tumors other than clear cell History of stroke within 6 months. History of abdominal fistula,perforation,or abscess within 6 months. Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have.

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: Intervention<br>In the phase I portion: Bevacizumab 10 mg/kg slow IV infusion on days 1 and 15 of each 28-day course Erlotinib 150 mg orally daily Imatinib 300 mg orally daily or 400 mg orally daily In the phase II portion: Bevacizumab 10 mg/kg 30-60 minute IV infusion on days 1 and 15 of every 28 day cycle Erlotinib 150 mg orally daily Imatinib 400 mg orally daily | Drug: Bevacizumab<br>* 10mg/kg IV infusion every 2 weeks<br>* Other names: Avastin;Drug: Erlotinib<br>* 150 mg po daily<br>* Other names: Tarceva;Drug: Imatinib<br>* 400-600mg daily<br>* Other names: STI571, Gleevec, Glivec, imatinib mesilate (INN);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 18 months | 
| Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease |  | 18 months | 
| Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bevacizumab, Recurrent clear cell renal cell carcinoma, Erlotinib, Imatinib