Urokinase-Plasminogen Activator (uPA) Inhibitor WX-UK1 in Combination With Capecitabine in Advanced Malignancies

Date de début de l'étude : 1 mai 2004

Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of a non-hematologic malignancy that is either unresponsive to currently available therapies or for which there is no known effective therapy. * Patient willing to give informed consent, understand and comply with study procedures/restrictions * Age\>=18 * Patients must have an ECOG performance status of 0, 1, or 2 * Life expectancy of \> 12 weeks * Negative serum pregnancy test for women of child-bearing potential and not nursing. Fertile patients must use effective contraception during and for 30 days (women) or 4 months (men) after treatment with WX-UK1. * Measurable or non-measurable disease. Patients without clinical or radiologic evidence of disease are not eligible. * Laboratory parameters (obtained within the screening period): WBC \>= 3 G/L, neutrophils \>= 1.5 G/L, platelets \>= 100 G/L, Hgb \>= 9 g/dL), total bilirubin \<= 1.5 x ULN, ASAT/ALAT/AP/GGT \<= 2.5 x ULN, serum creatinine \<= 2 x ULN. Exclusion Criteria: * History of hypersensitivity to the study drugs or chemically related compounds or any of the excipients * History of or current neurological disorder, in particular an active or treated seizure disorder * Known standard therapy for the patient's disease that is potentially curative or known to extend life expectancy. * Carcinomatous meningitis or untreated/uncontrolled metastatic brain parenchymal disease. * Concurrent or prior (within 4 weeks prior to start of WX-UK1 treatment for cytotoxic chemotherapy, biological-, endocrine-, investigational- or radiotherapy and 6 weeks for nitrosoureas, mitomycin-C) * Uncontrolled infection * Significant cardiac disease (NYHA classification III or IV * Contraindication to an infusion volume of 1000 ml over 2 h * History of or current blood coagulation disorders * History of or current bleeding disorder (including cerebral bleeding, recurrent massive nose bleeds, hematuria or unexplained bruising) * Diabetes mellitus, if not controlled by insulin, oral anti-diabetic agents or diet alone * Anticoagulant or thrombolytic therapy within four weeks prior to start of treatment (except heparin flush to keep a port open or coumadin 1 mg/day or ASA 100mg/d) * Active serious illness that renders the patient unsuitable for study entry or multiple blood sampling * Illness or condition that might alter the absorption, distribution, metabolism and elimination of WX-UK1 * Known Hepatitis B/C or HIV infection * Contraindication to capecitabine intake as specified in the SPC such as DPD-deficiency or concomitant intake of sorivudine or sorivudine related compounds * Known hemorrhagic brain metastasis