Bevacizumab and Polyethyleneglycol-7-Ethyl-10-Hydroxycamptothecin in Treating Patients With Refractory Solid Tumors

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