• Maximum tolerated dose [ Designated as safety issue: Yes ]
  
• Pharmacokinetics of bevacizumab and AZD2171 [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  

• Vascular endothelial growth factor expression in malignant effusions [ Designated as safety issue: No ]
  
• Response rate [ Designated as safety issue: No ]
  
• Association between nitric oxide and blood pressure [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the safety and toxicity of bevacizumab and AZD2171 in patients with metastatic or unresectable solid tumor or lymphoma.
• Determine the pharmacokinetic profile of this regimen in these patients.

Secondary

• Correlate serum concentrations of nitric oxide (NO) and NO synthase with vascular endothelial growth factor (VEGF) expression in patients treated with this regimen.
• Evaluate changes in tumor vasculature detected by dynamic contrast-enhanced MRI in patients treated with this regimen.
• Determine the potential predictive role of angiogenesis molecular endpoints (e.g., VEGF) in malignant effusion samples.
• Determine, preliminarily, the efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral AZD2171 once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bevacizumab and AZD2171 until the maximum tolerated dose (MTD) 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.

Blood samples are acquired at baseline, on day 2, and after 2 courses of treatment for pharmacokinetic studies. Samples are analyzed by TUNEL, immunofluorescence staining, laser-scanning cytometry, flow cytometry, enzyme-linked immunosorbent assay, and immunohistochemistry to assess apoptosis in tumor and endothelial cells, microvessel density mean vessel volume, nitric oxide concentration, and signal transduction pathways (i.e., ERK ½, P38 mitogen-activated protein kinase, protein kinase B, circulating endothelial and progenitor cells, basic fibroblast growth factor, vascular endothelial growth factor (VEGF) receptor phosphorylation, VEGF, and hypoxia inducible factor-1α). Patients also undergo tissue biopsy at baseline and after 2 courses of treatment for characterization of vascular and angiogenesis markers. Some patients also undergo DCE-MRI at baseline, once between days 22-24, and after every 2 courses of treatment to assess blood perfusion.

After completion of study treatment, patients are followed for 6 weeks.

PROJECTED ACCRUAL: A total of 51 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic or unresectable solid tumor or lymphoma

  • If assessing a single target lesion, histological confirmation of that particular lesion is required

• Stable brain metastasis allowed provided the following criteria are met:

  • Stable disease on MRI ≥ 4 weeks after completion of whole brain radiation
  • No evidence of progression on MRI 4 weeks after completion of stereotactic radiosurgery
  • Brain metastasis was completely excised
• No squamous cell non-small cell lung carcinoma

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 2.0 mg/dL (unless Gilbert's syndrome is present)
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5.0 times ULN if due to liver involvement)
• Serum creatinine ≤ 2.0 mg/dL
• Proteinuria < 1+ by dipstick or urine analysis
• Urine protein:creatinine ratio < 1.0 OR urine protein < 1,000 mg by 24-hour urine collection
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• No significant traumatic injury within the past 28 days
• No QTc prolongation (i.e., QTc > 500 msec) or other significant ECG abnormality within the past 14 days
• No serious or non-healing wound, ulcer, or bone fracture
• No bleeding diathesis, defined as PT and aPTT ≥ 1.5 times ULN or INR ≥ 1.5
• No active gastric or duodenal ulcer
• No uncontrolled systemic vascular hypertension, defined as systolic blood pressure (BP) > 140 mm Hg and diastolic BP > 90 mm Hg
• No concurrent uncontrolled illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics
• No conditions requiring drugs or biologics with proarrhythmic potential

• No clinically significant cardiovascular disease, including the following:

  • Cerebrovascular accident within the past 6 months
  • Myocardial infarction or unstable angina within the past 6 months
  • New York Heart Association class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Unstable angina pectoris
  • Clinically significant peripheral vascular disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• More than 28 days since prior major surgeries or open biopsy
• More than 7 days since prior core biopsy
• No concurrent major surgery
• No other concurrent investigational agents