An Open Label, Non Randomized , One Sequence, Add-On Study to Investigate the Effects of PTK787/ZK 222584 on the Pharmacokinetics and Pharmacodynamics of Warfarin at Steady-States in Cancer Patients

Fecha de inicio: 1 de mayo de 2004

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 \[St. John's wort\])