Rapamycin Plus Bevacizumab in Advanced Cancers

This is an interventional treatment trial for Advanced Cancer Read More

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