Warfarin and Vatalanib in Treating Patients With Advanced Solid Tumors

Inclusion Criteria:

• Histologically confirmed advanced solid tumor

• Progressed despite standard therapy OR no known standard therapy exists

  -- Currently receiving OR a candidate for prophylactic low-dose warfarin (1 mg/day)

• INR ≤ 1.4
• Must be an extensive metabolizer of CYP2C9 (at least 1 wild type allelle: *1)
• 18 and over
• Hemoglobin ≥ 9 g/dL

• AST and ALT ≤ 3 times upper limit of normal (ULN)

  • Bilirubin ≤ 1.5 times ULN
  • Albumin ≥ 3.0 g/dL
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody negative
  • Creatinine ≤ 1.5 ULN OR
  • Creatinine clearance > 50 mL/min
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• More than 14 days since prior anticancer chemotherapy
• More than 14 days since prior anticancer hormonal therapy
• More than 14 days since prior anticancer radiotherapy
• More than 14 days since other prior anticancer therapy
• More than 30 days since prior investigational drugs
• No ethanol for 2 days prior to and for the first 17 days of study treatment

Exclusion Criteria:

• No poor metabolizers of CYP2C9 (2 alleles of either *2 or *3)
• brain metastases
• history of or active coagulation disorders
• significant risk for bleeding
• uncontrolled high blood pressure (BP), defined as diastolic BP > 90 mm Hg or systolic BP > 140 mm Hg
• history of cerebral or aortic aneurysm
• pregnant or nursing
• recent history or evidence of drug or alcohol abuse
• active peptic ulcer disease or gastrointestinal bleeding
• contraindication or allergy to warfarin or related compounds
• risk for adverse events related to prolonged PT/PTT due to warfarin administration
• other medical condition that would preclude study participation
• concurrent chemotherapy
• concurrent hormonal therapy
• concurrent radiotherapy
• other concurrent CYP2C9 substrates or inhibitors
• concurrent CYP3A4 inducers or inhibitors
• concurrent food or dietary supplement known to alter the metabolism of CYP3A4 (e.g., grapefruit or Hypericum perforatum [St. John's wort])