Temsirolimus and Bevacizumab in Treating Patients With Stage III or Stage IV Malignant Melanoma

Inclusion Criteria

• Histologically or cytologically confirmed melanoma
• Stage III or IV disease
• Recurrent disease allowed
• Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm with conventional techniques OR ≥ 10 mm with spiral CT scan
• Tumor lesions in previously irradiated areas are not considered measurable disease
• Prior brain metastases allowed provided all of the following criteria are met:
• No more than a total of 5 brain metastases
• All metastases are no more than 2.5 cm
• Surgically resected or have been treated with gamma-knife or stereotactic radiosurgery
• More than 30 days since prior disease progression
• More than 30 days since prior steroids for managing brain metastases
• Concurrent steroids for other reasons allowed provided the dose is 1.5 are allowed provided the following criteria are met:
• In-range INR (usually between 2 and 3.5) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
• No active, clinically significant bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
• Minimal tumor bleeding of the skin allowed at the clinician's discretion
• No concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of the following:
• Temsirolimus
• Bevacizumab
• CYP450 isoenzymes
• No concurrent nonstudy-related surgical procedures
• No other concurrent anticancer agents or therapies

Exclusion Criteria

• Participants who have received these medications or treatments at any time ≤ 4 weeks of registration:
• Chemotherapy
• Radiotherapy to non-target lesions and lesions that are not to be biopsied. Prior radiotherapy to target lesions or lesions to be biopsied/resected is not permitted
• Immunotherapy
• Cytokine therapy
• Investigational reagents
• Invasive procedures defined as follows:
• Major surgical procedure, open biopsy or significant traumatic injury
• Anticipation of need for non-study related surgical procedures from registration until Cycle 26 (One year).
• Enzyme-inducing antiepileptic drugs (EIAEDs) or any other CYP3A4 inducer (Appendix C).

OR Participants who have not recovered from adverse events resulting from the administration of these agents/procedures > 4 weeks prior to registration.

• Participants who have received nitrosureas or mitomycin C ≤ 6 weeks of registration.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CCI-779 or bevacizumab, or with known hypersensitivity to Chinese hamster ovary cell products (t-PA) or other recombinant human antibodies (e.g., Remicade®).
• Participants who have previously received CCI-779, rapamycin, bevacizumab, or systemic therapies targeted primarily to VEGF, VEGF receptors, or to mTOR inhibition.
• Participants who have experienced any of the following ≤ 4 weeks prior to registration:
• Uncontrolled intercurrent illness
• Infection, CTCAE3 grade 3 or 4 (either ongoing, chronic, or active infection)
• Abdominal fistula
• Gastrointestinal perforation
• Intra-abdominal abscess
• Serious or non-healing wound
• Serious or non-healing ulcer
• Serious or non-healing bone fracture.
• Potential subjects with clinically significant cardiovascular disease
• Recent history (defined as ≤ 6 months of registration) of thromboembolic events including cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial ischemia, myocardial infarction (MI)
• Uncontrolled hypertension (hypertension despite maximal therapy)
• Unstable angina ≤ 6 months of registration
• New York Heart Association Classification of ≥ class II heart disease
• Congestive heart failure
• Serious cardiac arrhythmia requiring medication
• Clinically significant peripheral vascular disease
• Have a history of stroke
• Have an artificial valve, pace-maker, or similar device
• Psychiatric illness/socia