Imatinib Mesylate and Bevacizumab in Treating Patients With Advanced Melanoma or Other Advanced Cancers

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of 1 of the following:

  • Metastatic or unresectable malignancy for which standard curative or palliative measures do not exist or are no longer effective (phase I) (phase I study closed to accrual as of 8/23/04)
  • Melanoma (phase I and II)
• Measurable disease (phase II)
• No history or clinical evidence of CNS disease, including primary brain tumor or brain metastases
• Performance status - ECOG 0-1
• More than 3 months
• WBC at least 3,000/mm^3
• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No history of bleeding diathesis or coagulopathy
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN
• INR no greater than 1.5
• APTT normal
• Creatinine no greater than 2.0 times ULN
• Creatinine clearance at least 40 mL/min
• No proteinuria
• Urinary protein less than 500 mg/24 hours
• No history of stroke

• No uncontrolled hypertension within the past 6 months

  • Blood pressure less than 150/100 mm Hg on a stable antihypertensive regimen

• None of the following within the past 6 months:

  • Myocardial infarction
  • Unstable angina
  • New York Heart Association class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Grade II or greater peripheral vascular disease
  • Transient ischemic attack
  • Cerebrovascular accident
  • Other arterial thromboembolic event
  • Other clinically significant cardiovascular disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for at least 3 months after study participation
• No seizures not controlled with standard medical therapy
• No prior allergic reactions attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biological composition to imatinib mesylate
• No serious, nonhealing wound, ulcer, or bone fracture
• No ongoing or active infection requiring parenteral antibiotics
• No significant traumatic injury within the past 28 days
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent uncontrolled illness
• More than 4 weeks since prior immunotherapy
• More than 8 weeks since prior monoclonal antibody therapy
• No concurrent prophylactic granulocyte or platelet colony-stimulating factors
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No more than 1 prior cytotoxic chemotherapy regimen for advanced disease (phase II)
• More than 4 weeks since prior radiotherapy
• More than 28 days since prior major surgical procedure or open biopsy
• Recovered from prior therapy
• No concurrent chronic daily aspirin (greater than 325 mg/day) or nonsteroidal anti-inflammatory drugs known to inhibit platelet function
• No recent or concurrent full-dose anticoagulants (except as required to maintain patency of preexisting permanent indwelling IV catheters) or thrombolytic agent
• No concurrent grapefruit juice
• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational or commercial agents or therapies directed at the malignancy
• No other concurrent investigational agents