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