Rapamycin Plus Bevacizumab in Advanced Cancers

Inclusion Criteria:

* Metastatic or unresectable solid tumor for which standard treatments do not exist or are no longer effective
* Performance status of 0-1
* Measurable or non-measurable disease
* Life expectancy of at least 12 weeks
* No anticipated need of other cancer treatments within the next 4 weeks
* 18 years or older
* Negative pregnancy test for women able to have children, agreement to use a medically accepted birth control method while receiving the study drugs and for at least 2 weeks after stopping, not breast feeding
* Ability to understand and willingness to sign a written informed consent document
* No evidence of bleeding diathesis
* Patients without lung cancer receiving anti-coagulation treatment can participate
* Adequate organ and marrow function:

  * ALT and AST less than or equal to 2.5 times the institutional ULN (less than 5 times for patients with liver involvement)
  * hemoglobin at least 9g/dL
  * absolute neutrophil count at least 1,500/µL
  * platelets at least 100,000/µL
  * total bilirubin less than or equal to 1.5 times the institutional ULN
  * creatinine less than or equal to 1.5 times the institutional ULN

Exclusion Criteria:

* Prior treatment with both bevacizumab and an mTOR inhibitor is not allowed. Prior treatment with both bevacizumab OR mTOR inhibitor (including rapamycin) is allowed. Patients who had a grade 3 or greater side effect with either bevacizumab or an mTOR inhibitor cannot take part in this study.
* Chemotherapy or Immunotherapy within the 4 weeks of study start
* Radiotherapy within 14 days of study start
* Cannot be receiving any other investigational drugs or any other cancer treatments while on study (with the exception of androgen ablating agents for patients with prostate cancer).
* Patients with squamous non-small cell lung cancer (NSCLC)
* Patients with lung cancer or lung metastases:

  * on full dose anticoagulation
  * taking 325mg aspirin per day
  * on non-steroidal anti-inflammatory agents
* HIV positive patients receiving combination anti-retroviral therapy are excluded due to potential for serious infections while taking marrow suppressing agents
* Ongoing illness or medical exclusions, including but not limited to:

  * active or ongoing infection
  * symptomatic congestive heart failure
  * uncontrolled hypertension despite optimal medical management
  * cardiac arrhythmia except paroxysmal atrial fibrillation
  * psychiatric illness/social situations that would limit compliance with study requirements
  * history of organ allograft, bone marrow or peripheral blood stem cell transplant
  * known or suspect allergy to bevacizumab or rapamycin
  * seizure disorder treated with steroid or anticonvulsant therapy
  * thrombotic or embolic events within 6 months of starting study
  * pulmonary hemorrhage/bleeding within 12 weeks of starting study (grade 3 event within 4 weeks of first dose of drug). Patients with a history of pulmonary hemorrhage/bleeding cannot be on full dose anticoagulation.
  * pulmonary fibrosis or interstitial lung disease
  * serious non-healing wound, ulcer or bone fracture
  * Major surgery, open biopsy or a traumatic injury within 4 weeks of starting study drug
  * anticipated need for major surgery while on-study
  * current use of any herbal supplements or rifampin (rifampicin)
  * prior history of hypertensive crisis or hypertensive encephalopathy
  * history of myocardial infarction or unstable angina within 6 months of starting study
  * known CNS disease
  * significant vascular disease
  * symptomatic peripheral vascular disease
  * evidence of bleeding diathesis or coagulopathy
  * core biopsy or other minor surgical procedure (except placement of vascular access device) within 7 days of starting study
  * history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of study start
  * proteinuria at screening