• Safety and toxicity by physical exam, history, patient diary, blood pressure (BP) monitoring, and clinical blood and urine tests at baseline and every 2 weeks (BP daily) [ Designated as safety issue: Yes ]
  
• Resp. to tx at max. tol. dose of sorafenib+bevacizumab by biochem. chges in Ras-Raf-MAPK & VEGF signal transduction pathways by tumor lys. microarray of biopsied tumor & stromal cells at baseline, 2 wks after monotx, and after 2 wks of combo tx [ Designated as safety issue: No ]
  

• Pharmacoproteomic effect of combotx on mol. sig. events compared to monotx focused on angiogenesis, survival, & apoptotic pathways by tumor lys. array of biopsied tumor and stroma at baseline, after 2 wks of monotx, and after 2 wks of combotx [ Designated as safety issue: No ]
  
• Pharmacokinetic effects as measured in serum samples immediately pre-dose, and at 0.25, 0.50, 1, 2, 4, 6, 8, 12, and 24 hours after ingestion of study treatment day 1 of courses 1 and 2 for cohort 2 [ Designated as safety issue: No ]
  
• Pharmacogenomics evaluation of sorafenib by genotyping of CYP3S4/5 according to the Medical Oncology Clinical Research Unit (MOCRU) Clinical Pharmacokinetics core standard operating procedure (SOP) at baseline [ Designated as safety issue: No ]
  
• Correlation of identified genetic tumor mutations in Ras and Raf with clinical events as measured by tumor lysates array analysis at baseline, after 2 weeks of monotherapy, and after 2 weeks of combination therapy [ Designated as safety issue: No ]
  
• Correlation of changes in VEGF and other angiogenic cytokines in plasma with clinical outcomes at baseline, every 2 weeks for 2 months, and then monthly [ Designated as safety issue: No ]
  
• Tumor vascularity as evaluated by Dynamic Contrast Enhanced Magnetic Resonance Imaging at baseline and weeks 2, 4, and 6 [ Designated as safety issue: No ]
  
• Tumor vascularity as evaluated by positron-emission tomography at baseline and weeks 2 and 6 [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of sorafenib and bevacizumab in patients with refractory, metastatic, or unresectable solid tumors.
• Determine the safety and toxicity of this regimen in these patients.
• Determine biochemical changes in the Ras-Raf-MAPK and VEGF signal transduction pathways in tumor and stromal cells from patients treated with this regimen.

Secondary

• Determine the pharmacokinetic effects of this regimen in these patients.
• Correlate genetic mutations in Ras and Raf in tumor tissue with clinical events in patients treated with this regimen.
• Correlate changes in VEGF and other angiogenic cytokines in plasma with clinical outcomes of patients treated with this regimen.

OUTLINE: This is an open-label, dose-escalation study followed by a randomized study.

• Part 1: Patients receive oral sorafenib once daily on days 1-28 OR once daily on days 1-5, 8-12, 15-19, and 22-26 and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of sorafenib and bevacizumab until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

• Part 2: Patients are randomized to 1 of 2 treatment arms for course 1.

  • Arm I: Patients receive oral sorafenib at the MTD once daily on days 1-21.
  • Arm II: Patients receive bevacizumab IV at the MTD over 30-90 minutes on days 1 and 15.

Beginning in course 2, all patients receive oral sorafenib twice daily on days 1-21 and bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor malignancy

  • Metastatic, refractory, or unresectable disease
  • No known standard curative therapies exist or are no longer effective
• At least 1 lesion amenable to biopsy (part 2 only)
• No squamous cell carcinoma of the lung
• No history of any type of primary lung cancer with hemoptysis

• No brain metastases

  • Prior remote CNS metastases allowed at the discretion of the investigator provided patient has undergone curative therapy (e.g., radiotherapy, gamma knife therapy, or surgery) and has remained disease free for ≥ 2 years

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,200/mm^3
• Platelet count ≥ 100,000/mm^3
• No evidence of bleeding diathesis

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• PTT < 1.25 times ULN
• PT < 1.25 times ULN OR
• INR < 1.25 times ULN

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 45 mL/min
• Urine protein:creatinine ratio < 0.5 OR urine protein < 1,000 mg on 24-hour urine collection

Cardiovascular

• No thrombotic or embolic event within the past 6 months, including any of the following:

  • Cerebrovascular accident
  • Transient ischemic attack
  • Unstable angina pectoris
  • Myocardial infarction
  • Deep vein thrombosis
• No New Heart Association class II-IV symptomatic congestive heart failure
• No cardiac arrhythmia
• No hypertension, defined as systolic blood pressure (BP) > 140 mm Hg or diastolic BP > 90 mm Hg despite optimal medical management

Pulmonary

• See Disease Characteristics
• No pulmonary embolism within the past 6 months
• No hemoptysis

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 2 months after study participation
• Amylase and lipase normal
• Able to swallow tablets
• No ongoing or active infection
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No history of high-grade varices
• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses within the past 28 days
• No serious nonhealing wound, including wounds healing by secondary intention
• No acute or nonhealing ulcers
• No bone fracture within the past 3 months
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 4 weeks since prior biologic therapy
• At least 8 weeks since prior monoclonal antibody therapy
• No prior bevacizumab

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin, or carboplatin)

Endocrine therapy

• Patients with prostate cancer must continue to receive luteinizing hormone-releasing hormone agonist unless orchiectomy has been performed
• More than 4 weeks since prior hormonal therapy

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy

Surgery

• See Endocrine therapy
• See Disease Characteristics
• More than 4 weeks since prior surgery

Other

• Recovered from all prior therapy
• At least 7 days since prior and no concurrent complementary therapy
• At least 7 days since prior antibiotic therapy for active infection
• No prior sorafenib
• No concurrent therapeutic anticoagulation therapy (e.g., warfarin, heparin, or heparinoids)
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent complimentary or alternative therapy unless approved by the investigator
• No concurrent over-the-counter agents unless approved by the investigator