Sorafenib and Bevacizumab in Treating Patients With Advanced Kidney Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed renal cell carcinoma (RCC) of 1 of the following types*:

  • Clear cell
  • Papillary (phase I only)
  • Chromophobe (phase I only)
  • Sarcomatoid (phase I only) NOTE: *Clear cell RCC with < 25% of any other histology (e.g., papillary, chromophobe, or oncocytic) required for enrollment in the phase II portion of the study
• Advanced disease
• Measurable disease not curable by standard therapy (for patients in the phase I portion of the study only)
• Measurable disseminated disease that is not curable by standard radiotherapy or surgery (for patients in the phase II portion of the study only)

• Has undergone prior nephrectomy, unless 1 of the following is true (for patients in the phase II portion of the study only):

  • Primary tumor ≤ 5 cm
  • Extensive liver metastases (i.e., > 30% of liver parenchyma) OR multiple bone metastases (i.e., > 5) OR extensive extrarenal tumor or unresectable local/regional tumor extension making nephrectomy a clinically questionable and unreasonable procedure
• Tumor tissue block available (for patients in the phase II portion of the study only)

• No history or clinical evidence of CNS disease, including primary brain tumor (history of meningioma allowed), or brain metastasis

  • Patients with a history of brain metastasis that have been resected or have had radiosurgery with no progression for man than 6 months are eligible

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• Hemoglobin ≥ 9.0 g/dL (transfusion allowed)
• WBC ≥ 3,000/mm^3
• Absolute granulocyte count ≥ 1,200/mm^3
• Platelet count ≥ 100,000/mm^3
• No history of bleeding diathesis or coagulopathy

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• INR ≤ 1.5
• aPTT ≤ 1.3 times ULN

Renal

• Creatinine ≤ 1.5 times ULN (2.0 times ULN for patients in the phase II portion of the study) OR
• Creatinine clearance ≥ 40 mL/min
• Urine protein < 1+ by dipstick OR ≤ 1,000 mg by 24-hour urine collection

Cardiovascular

• No uncontrolled hypertension

  • Blood pressure must be ≤ 150/90 mm Hg on a stable antihypertensive regimen

• No clinically significant cardiovascular disease within 1 year prior to study entry

  • No myocardial infarction within the past 6 months
  • No unstable angina pectoris within the past 6 months
  • No New York Heart Association grade II-IV congestive heart failure
  • No serious cardiac arrhythmia requiring medication
• No peripheral vascular disease ≥ grade 2 within the past year
• No history of stroke
• No other clinically significant cardiovascular disease

Other

• Not pregnant
• No nursing during and for ≥ 3 months after completion of study treatment
• Negative pregnancy test
• Fertile patients must use effective contraception prior to, during, and for ≥ 3 months after completion of study treatment
• No condition that would preclude ability to swallow pills
• No other malignancy within the past 3 years with the exception of non-melanoma skin cancer, melanoma in situ, cervical cancer, ductal carcinoma in situ, or lobular carcinoma in situ (for patients in the phase II portion of the study only)
• No prior malignancy that does not have a very likely cure rate (i.e., approximately 75% or greater) (for patients in the phase II portion of the study only)
• No history of allergic reaction attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biological composition to sorafenib
• No psychiatric illness or social situation that would preclude study compliance
• No serious non-healing wound, ulcer, or bone fracture
• No history or clinical evidence of uncontrolled seizures
• No significant traumatic injury within the past 28 days
• No ongoing or active infection requiring parenteral antibiotics
• No other uncontrolled illness
• No history of seizures unless controlled with standard medical therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior immunotherapy
• More than 8 weeks since prior monoclonal antibodies
• No more than 1 prior vaccine or cytokine-based immunotherapy regimen for stage IV disease (for patients in the phase II portion of the study only)
• No prior vascular endothelial growth factor (VEGF) or VEGF signaling inhibitors
• No prior bevacizumab or sorafenib
• No other prior antiangiogenic therapy (e.g., SU011248, ZD6474, or VEGF Trap)
• Prior thalidomide or interferon alfa as adjuvant therapy or for treatment of stage IV disease allowed
• No concurrent prophylactic granulocyte or platelet colony-stimulating factors

Chemotherapy

• More than 4 weeks since prior chemotherapy

• No prior chemotherapy regimen for stage IV disease (for patients in the phase II portion of the study only)

  • Prior immunotherapy is not considered chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 2 weeks since prior radiotherapy and recovered

Surgery

• See Disease Characteristics
• More than 4 weeks since prior major surgical procedure or open biopsy
• No concurrent major surgery

Other

• No prior MAP kinase pathway inhibitors (for patients in the phase II portion of the study only)
• No prior experimental therapy for advanced RCC (for patients in the phase II portion of the study only)

• No concurrent or recent (within 7 days of starting study drugs) use of full-dose anticoagulants or thrombolytic agents

  • Concurrent anticoagulants to maintain patency of preexisting, permanent indwelling IV catheters allowed
  • Concurrent warfarin allowed provided INR ≤ 1.5
• No concurrent P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, phenobarbital, rifampin, or Hypericum perforatum [St. John's wort])
• No concurrent combination anti-retroviral therapy for HIV-positive patients