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

• Maximum tolerated dose
• Pharmacokinetics of bevacizumab and AZD2171
• Toxicity

• 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 ]

• Vascular endothelial growth factor expression in malignant effusions
• Response rate
• Association between nitric oxide and blood pressure

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. AZD2171 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bevacizumab and AZD2171 may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving bevacizumab together with AZD2171 may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bevacizumab and AZD2171 in treating patients with metastatic or unresectable solid tumor, lymphoma, intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma.

OBJECTIVES:

Primary

• Determine the safety and toxicity of bevacizumab and AZD2171 in patients with metastatic or unresectable solid tumor, lymphoma, intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma.
• 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). Some 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.

• Brain and Central Nervous System Tumors
• Lymphoma
• Small Intestine Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

• Biological: bevacizumab
• Drug: cediranib maleate
• Genetic: TdT-mediated dUTP nick end labeling assay
• Other: flow cytometry
• Other: fluorescent antibody technique
• Other: immunohistochemistry staining method
• Other: laboratory biomarker analysis
• Other: pharmacological study
• Procedure: biopsy
• Procedure: dynamic contrast-enhanced magnetic resonance imaging

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:

  • Metastatic or unresectable solid tumor or lymphoma

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

  • Intracranial glioblastoma, gliosarcoma, or anaplastic astrocytoma meeting all of the following criteria:

    • Must have shown unequivocal radiographic evidence for tumor progression by MRI scan

    • Must be on a steroid dose that has been stable for at least 5 days

      • If the steroid dose is increased between the date of imaging and registration, a new baseline MRI 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