Interferon Alfa-2b With or Without Bevacizumab in Treating Patients With Advanced Renal Cell Carcinoma (Kidney Cancer)

Study Overview
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Brief Summary
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RATIONALE: Biological therapies, such as interferon alfa-2b, may interfere with the growth of tumor cells. Bevacizumab may stop the growth of tumor cells by stopping blood flow to the tumor. It is not yet known whether interferon alfa-2b is more effective with or without bevacizumab in treating advanced renal cell carcinoma (kidney cancer). PURPOSE: This randomized phase III trial is studying interferon alfa-2b and bevacizumab to see how well they work compared to interferon alfa-2b alone in treating patients with advanced renal cell carcinoma.

Detailed Description
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OBJECTIVES: Primary Compare the overall survival of patients with advanced renal cell carcinoma treated with interferon alfa-2b alone or interferon alfa-2b with bevacizumab. Secondary Compare the time to disease progression and objective response rates in patients treated with these regimens. Determine the toxicity of interferon alfa-2b in combination with bevacizumab in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior nephrectomy (yes vs no) and number of risk factors for disease progression (0 vs 1-2 vs 3 or more). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive interferon alfa-2b subcutaneously (SC) three times a week. Arm II: Patients receive interferon alfa-2b as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then annually for up to 10 years after study entry. PROJECTED ACCRUAL: A total of 700 patients (350 per treatment arm) will be accrued for this study within 3 years.

Official Title
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A Randomized Phase III Trial Of Interferon Alfa-2B Or Interferon Alfa-2B Plus Bevacizumab In Patients With Advanced Renal Carcinoma

Conditions
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Kidney Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Biological: recombinant interferon alfa


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed renal cell carcinoma (RCC) Conventional clear cell carcinoma Metastatic or unresectable disease The following characteristics and cellular types are excluded: True papillary Sarcomatoid features without a clear cell component Chromophobe Oncocytoma Collecting duct tumor Transitional cell carcinoma Measurable or nonmeasurable disease, including any of the following: Unidimensionally measurable lesion ≥ 20 mm by conventional techniques (e.g., physical exam or chest x-ray) OR 10 mm by spiral CT scan or MRI The following are considered nonmeasurable disease: Small lesions Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Irradiated lesions, unless progression is documented after radiotherapy RCC paraffin tissue blocks or unstained slides must be available No evidence of prior or concurrent CNS metastases by MRI or CT scan PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 70-100% Life expectancy Not specified Hematopoietic Granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No history of clinically significant bleeding Hepatic AST/ALT ≤ 2.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Bilirubin ≤ 1.5 times ULN Renal Creatinine ≤ 1.5 times ULN No proteinuria > 1+ Proteinuria ≥ 2+ allowed provided protein is < 2 g/24-hour urine collection Cardiovascular No deep venous thrombosis within the past year No cerebrovascular accident within the past year No peripheral vascular disease with claudication on < 1 block No uncontrolled hypertension defined as blood pressure ≥160 mm Hg (systolic) and/or ≥ 90 mm Hg (diastolic) while on medication No New York Heart Association class II-IV congestive heart failure No angina pectoris requiring nitrate therapy No myocardial infarction within the past 6 months No other significant cardiovascular disease Pulmonary No pulmonary embolus within the past year No ongoing hemoptysis Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study treatment No preexisting thyroid abnormality in which normal thyroid function cannot be maintained by medication No delayed wound healing, ulcers, or bone fractures No uncontrolled psychiatric disorder No other currently active* malignancy except nonmelanoma skin cancer NOTE: *Disease is not considered currently active if patient completed anticancer therapy and is considered to have < 30% risk of relapse PRIOR CONCURRENT THERAPY: Biologic therapy No prior systemic immunotherapy for RCC No prior thalidomide, anti-vascular endothelial growth factor (VEGF) therapy, VEGF receptor inhibitors, or antiangiogenic treatment of any kind No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF) Chemotherapy No prior systemic chemotherapy for RCC No concurrent chemotherapy Endocrine therapy No concurrent systemic corticosteroid therapy except the following: Topical and inhaled steroids Replacement therapy for adrenal insufficiency No concurrent hormones except those administered for nondisease-related conditions (e.g., insulin for diabetes) Radiotherapy See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered Prior palliative radiotherapy to metastatic lesions allowed provided at least 1 measurable or nonmeasurable lesion remains untreated No concurrent palliative radiotherapy Surgery At least 4 weeks since prior major surgery and recovered Other No other prior systemic investigational therapy for RCC No other prior adjuvant or neoadjuvant systemic therapy for RCC No concurrent full-dose oral or parenteral anticoagulation* NOTE: *Low-dose (1 mg) warfarin for maintenance of catheter patency and/or daily prophylactic aspirin is allowed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interferon<br>Treatment with interferon alfa 2b | Biological: recombinant interferon alfa<br>* 9 million units subQ injection 3 x/week for 4 weeks<br>|
| Experimental: Interferon + bevacizumab<br>Addition of bevacizumab to interferon alfa 2b treatment | Biological: bevacizumab<br>* 10mg/kg IV infusion on Days 1 & 15 of each cycle<br>Biological: recombinant interferon alfa<br>* 9 million units subQ injection 3 x/week for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  | q 3 cycles | 
| Toxicity |  | q cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV renal cell cancer, clear cell renal cell carcinoma, recurrent renal cell cancer