The purpose of this study is to determine the safety, tolerability, maximum tolerated dose
(MTD), pharmacokinetics, and pharmacodynamics of the combination of WX-UK1 and capecitabine
in patients with advanced malignancies.
- 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
- 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.
- 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
- 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
- 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
- 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