A Pilot Study of Weekly EZN-2208 (PEGylated SN-38) in Combination With Bevacizumab in Refractory Solid Tumors

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed solid tumors

- Metastatic or unresectable disease for which standard therapies do not exist or
are no longer effective

- No known CNS disease

- Treated brain metastasis not requiring steroids and with no evidence of
progression or hemorrhage after treatment for ≥ 3 months, as ascertained by
clinical examination and brain imaging (MRI or CT scan), allowed

- Treatment for brain metastases may include whole-brain radiotherapy (WBRT),
radiosurgery (RS; Gamma Knife, LINAC, or equivalent), or a combination as
deemed appropriate by the treating physician

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2 (Karnofsky 60-100%)

- Life expectancy > 3 months

- WBC ≥ 3,000/mm³

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

- Urine protein: proteinuria 2+ OR < 1,000 mg on 24-hour urine collection

- Fertile patients must use effective contraception (hormonal, barrier method of birth
control, or abstinence) prior to, during, and for 3 months after completion of study

- Not pregnant or nursing

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to polyethyleneglycol-7-ethyl-10-hydroxycamptothecin (EZN-2208)
or bevacizumab

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Clinically significant cardiovascular disease

- Inadequately controlled hypertension (systolic BP > 160 mm Hg and/or
diastolic BP > 90 mm Hg despite antihypertensive medication)

- History of stroke and/or cerebrovascular accident within the past 6 months

- Myocardial infarction or unstable angina within the past 6 months

- NYHA grade II-IV congestive heart failure

- Serious and inadequately controlled cardiac arrhythmia

- Significant vascular disease (e.g., aortic aneurysm, history of aortic
dissection)

- Clinically significant peripheral vascular disease

- Psychiatric illness/social situations that would limit compliance with study
requirements

- No serious or non-healing wound, ulcer, or bone fracture

- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within the past 6 months

- No significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
recent peripheral arterial thrombosis) within the past 6 months

- No evidence of bleeding diathesis or coagulopathy

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

PRIOR CONCURRENT THERAPY:

- More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas
or mitomycin C) and recovered

- There are no restrictions on prior therapy

- At least 2 weeks since receiving study drug as a participant in a phase 0 study
(or early phase I)

- No major surgical procedure, open biopsy, or significant traumatic injury within the
past 28 days, and no anticipation of need for major surgical procedures during the
course of the study

- No other concurrent investigational agents

- No other concurrent chemotherapy

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent enzyme-inducing anti-epileptic drugs (EIAED)

- Patients on non-EIAED allowed at the discretion of principal investigator

- No concurrent anticoagulation therapy