Phase I Clinical Trial Evaluating the Toxicity, Pharmacokinetics and Biological Effect of Intravenous Bevacizumab (Avastin TM) in Combination With Escalating Doses of Oral AZD2171 for Patients With Advanced Malignancies

Inclusion Criteria:

- Patients must have histological confirmation of Solid Tumor or Lymphoma that is
metastatic or unresectable; if assessing a single target lesion, histological
confirmation of that particular lesion MUST be carried out

- Patients may have received an unlimited number of prior therapies; however, At least
4 weeks MUST have passed since the last chemotherapy to day 1 of registration (6
weeks for regimens containing nitrosoureas or Mitomycin C)

- ECOG performance status =< 2 (Karnofsky >= 60%)

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin =< 2.0 mg/dL (does NOT apply to patients with Gilbert's Syndrome)

- AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal (Patients with liver
involvement will be allowed =< 5.0 X institutional upper normal limit)

- Serum creatinine =< 2.0 mg/dL

- Patients MUST have recovered from all treatment related toxicities to Grade 1 NCI CTC
(v 4.0) in severity

- Patients must be willing and able to review, understand, and provide written consent
before starting therapy

- Patients with stable brain metastasis (stable disease on one MRI assessment at least
4 weeks after completion of whole brain radiation, no evidence of progression on MRI
assessment 4 weeks after stereotactic radiosurgery or complete surgical excision)
will also be allowed to participate in this trial

- Patients with histologically proven intracranial glioblastoma, gliosarcoma or
anaplastic astrocytoma will be eligible; patients must have shown unequivocal
radiographic evidence for tumor progression by MRI scan; scan should be performed
within 14 days prior to registration and 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

Exclusion Criteria:

- Patients with squamous non-small cell lung carcinoma

- Serious or non-healing wound, ulcer or bone fracture

- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
within 28 days of day 1 of registration

- Invasive procedures defined as follows:

- Major surgical procedure, open biopsy or significant traumatic injury within 28
days prior to Day 1 registration

- Anticipation of need for major surgical procedures during the course of the
study

- Core biopsy within 7 days prior to day 1 of therapy

- Patients may not be receiving any other investigational agents

- Patients with bleeding diathesis (clinical bleeding, prothrombin time >= 1.5 X upper
institutional normal value, INR >= 1.5, activated partial thromboplastin time aPTT >=
1.5 X upper institutional normal value), active gastric or duodenal ulcer

- Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg,
Diastolic Blood Pressure > 90 mmHg)

- Urine protein should be screened by dipstick or urine analysis; for proteinuria > 1+
or urine protein:creatinine ratio > 1.0, 24-hour urine protein should be obtained and
the level should be < 1000 mg for patient enrollment

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring parenteral antibiotics on Day 1

- Patients with clinically significant cardiovascular disease:

- History of CVA within 6 months

- Myocardial Infarction or unstable angina within 6 months

- New York Heart Association Grade II or greater congestive heart failure, serious
cardiac arrhythmia requiring medication, unstable angina pectoris

- Clinically significant peripheral vascular disease

- QTc prolongation > 500msec or other significant ECG abnormality noted within 14
days of registration

- Conditions requiring concurrent use of drugs or biologics with proarrythmic
potential; these drugs are prohibited during studies with AZD2171 (refer to
appendix V for a listing of these agents)

- Patients with history of hemoptysis

- Patients with tumor mass abutting a major vessel

- Pregnant women are excluded from this study because AZD-2171 is an angiogenesis
inhibiting agent with potential teratogenic or abortifacient effects; because of the
potential risk for adverse events in nursing infants secondary to treatment of the
mother with AZD-2171, breastfeeding should be discontinued if the mother is treated
with AZD-2171; these potential risks may also apply to other agents used in this
study; women of child-bearing potential and men must agree to use contraception prior
to study entry and for the duration of study participation; should a woman become
pregnant or suspect she is pregnant while participating in this study, she should
inform her treating physician immediately