Bevacizumab and Aldesleukin in Treating Patients With Metastatic Clear Cell Carcinoma of the Kidney

OBJECTIVES:

Primary

• To evaluate the effect of the combination of bevacizumab and aldesleukin on progression-free survival of patients with good- or intermediate-risk metastatic clear cell renal cell carcinoma.

Secondary

• To determine the objective response rate in patients receiving this regimen.
• To determine the time to progression in patients receiving this regimen.
• To evaluate immunomodulatory effects of this regimen in patients
• To evaluate the toxicity of this regimen in these patients.

OUTLINE: Patients receive bevacizumab IV over 30-90 minutes on days -14, 1, 15, 29, and 42 and aldesleukin subcutaneously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Courses repeat every 8 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving complete response after completion of study therapy may receive 1 additional course of therapy.

After completion of study therapy, patients are followed periodically.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed renal cell carcinoma (RCC) of clear cell histology with or without sarcomatoid features

• Metastatic disease
• No non-clear cell RCC (i.e., papillary, collecting-duct, or chromophobe)
• Good- or intermediate-risk category as defined by having ≤ 2 of the following factors:

• No prior nephrectomy
• Karnofsky performance status < 80%
• Hemoglobin < 12 g/dL
• Corrected calcium > 10.0 mg/dL
• LDH > 1.5 times upper limit of normal (ULN)
• Must have undergone a nephrectomy at least 28 days ago
• Measurable or evaluable disease by RECIST
• No significant effusions and/or ascites
• No prior or concurrent brain or CNS metastasis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy of ≥ 3 months
• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.5 g/dL
• Creatinine ≤ 2.0 mg/dL
• Total bilirubin ≤ 1.5 mg/dL
• AST ≤ 5.0 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN (≤ 10 times ULN with bone metastasis)
• Calcium ≤ 12 mg/dL
• Urine protein:creatinine ratio ≤ 1.0
• INR ≤ 1.5 (unless receiving warfarin therapy)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled seizure disorder
• No known HIV positivity
• No local or systemic infections requiring IV antibiotics within the past 28 days
• No significant traumatic injury in the past 28 days
• No serious non-healing wound, ulcer, or acute bone fracture
• No evidence of bleeding diathesis or coagulopathy
• No other malignancy except basal cell or squamous cell carcinoma of the skin, carcinoma in-situ of the uterine cervix, or any malignancy treated with curative intent and in complete remission for > 3 years
• No history of serious systemic or severe cardiovascular disease, including any of the following:

• Arterial thromboembolic event (including transient ischemic attack)
• Cerebrovascular accident
• Unstable angina
• Myocardial infarction within the past 6 months
• Uncontrolled hypertension (BP > 160/110 mm Hg on medication)
• Uncontrolled cardiac arrhythmia
• Congestive heart failure
• Angina pectoris
• NYHA class III-IV cardiovascular disease
• Peripheral vascular disease ≥ grade II
• No history of abdominal fistula and/or bowel or gastric perforation within the past 6 months
• No history of other diseases, metabolic dysfunction, or physical or laboratory examination findings giving reasonable suspicion of a disease or condition that contraindicate the use of investigational drugs, or that might affect the interpretation of study results, or that render patient at high-risk for treatment complications

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior organ allografts
• No prior systemic therapy for metastatic clear cell renal cell carcinoma
• At least 4 weeks since prior radiotherapy and recovered

• Radiotherapy for control of pain from skeletal lesions allowed within the past 28 days
• More than 12 months since prior adjuvant therapy
• More than 7 days since prior fine-needle aspirations or core biopsies
• More than 28 days since prior and no concurrent major surgery requiring general anesthesia or open biopsy
• No concurrent aspirin, corticosteroids (except at replacement doses), barbiturates, or other investigational agents