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

• Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  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.
• 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 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death [ Time Frame: 24 months ] [ Designated as safety issue: No ]

• Progression-free survival
• Overall survival.

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.

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.

• Drug: Bevacizumab
  10mg/kg IV infusion every 2 weeks
  Other Name: Avastin
• Drug: Erlotinib
  150 mg po daily
  Other Name: Tarceva
• Drug: Imatinib
  400-600mg daily
  Other Name: STI571, Gleevec, Glivec, imatinib mesilate (INN)

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.

• Genentech
• Novartis