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 \< that required for managing brain metastases
* Disease accessible for core needle biopsy, incisional biopsy, and/or surgical resection and meets one of the following criteria:

  * One large tumor deposit ≥ 5 cm³ from which biopsies can be harvested multiple times
  * Multiple deposits that can be biopsied or excised individually on different dates, measured as follows:

    * One lesion ≥ 5 cm\^3
    * Two lesions ≥ 3 cm\^3
    * Three lesions ≥ 2 cm\^3
* ECOG performance status 0-1
* Weight ≥ 110 pounds (without clothes)
* WBC ≥ 3,000 mm³
* Absolute neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Bilirubin normal
* AST and ALT ≤ 2.5 times upper limit of normal
* Creatinine normal OR creatinine clearance ≥ 60 mL/min
* Urine protein: creatinine ratio \< 1.0 OR 24-hour urine protein \< 1,000 mg
* Fasting cholesterol \< 350 mg/dL (cholesterol medications are allowed)
* Fasting triglycerides \< 400 mg/dL
* PT INR ≤ 1.5 (unless on full-dose anticoagulants)
* Hematocrit \< 41% (for males) or \< 38% (for females)
* None of the following within the past 4 weeks:

  * Uncontrolled intercurrent illness
  * Ongoing or active acute (CTCAE v.3 grade 3 or 4) infection
  * Abdominal fistula
  * Gastrointestinal perforation
  * Intra-abdominal abscess
  * Serious or nonhealing wound, ulcer, or bone fracture
* No psychiatric illness or social situations that would preclude study compliance
* No clinically significant cardiovascular disease, including the following:

  * Cerebrovascular accident within the past 6 months
  * Transient ischemic attack within the past 6 months
  * Myocardial ischemia within the past 6 months
  * Myocardial infarction within the past 6 months
  * Other thromboembolic event within the past 6 months
  * Unstable angina within the past 6 months
  * Uncontrolled hypertension (i.e., hypertension despite maximal therapy)
  * New York Heart Association class II-IV heart disease
  * Congestive heart failure
  * Serious cardiac arrhythmia requiring medication
  * Clinically significant peripheral vascular disease
  * History of stroke
  * Artificial valve, pacemaker, or similar device
* No uncontrolled diabetes

  * Hemoglobin A1c \< 7%
* No significant traumatic injury within the past 28 days
* No history of allergic reactions to compounds of similar chemical or biological composition to temsirolimus or bevacizumab
* No hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (e.g., infliximab)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
* HIV negative
* Hepatitis C negative
* See Disease Characteristics
* More than 4 weeks since any of the following prior treatments and recovered:

  * Chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  * Radiotherapy to nontarget lesions or lesions that are not to be biopsied
  * Immunotherapy
  * Cytokine therapy
  * Enzyme-inducing antiepileptic drugs (EIAEDs) or other CYP3A4 inducers
  * Investigational agents
* More than 4 weeks since prior major surgery or open biopsy and recovered
* No prior temsirolimus, rapamycin, bevacizumab, or systemic therapies targeted primarily to vascular endothelial growth factor (VEGF), VEGF receptors, or to mTOR inhibition
* Concurrent full-dose anticoagulants (e.g., warfarin/low molecular weight heparin) with PT INR \> 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/social situations that would limit compliance with study requirements.
* Pregnant (positive pregnancy test) or nursing women. Both fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 6 months after the completion of their participation in the study therapy.
* PT INR \> 1.5, (unless the potential subject is on full dose anticoagulants and meet criteria described in Section 3.1.8).
* Participants with uncontrolled diabetes, defined as having a HGBA1C ≥ 7%.