A Phase I/II Safety, Pharmacodynamic, and Pharmacokinetic Study of Intravenously Administered PXD101 Plus Carboplatin or Paclitaxel or Both in Patients With Advanced Solid Tumours

Inclusion Criteria:

- Ovarian patients:

-- Patients with epithelial ovarian, primary peritoneal, fallopian tube or mixed
mullerian cancer of ovarian origin in need of relapse treatment

- Bladder patients:

-- Patients with urothelial (transitional cell) cancer of the bladder

- All Patients:

- At least one measurable uni-dimensional lesion

- ECOG (Eastern Cooperative Oncology Group) status ≤ 2

- Life expectancy ≥ 3 months

- Age ≥ 18 years

- Acceptable liver, renal and bone marrow function:

- Bilirubin ≤ 1.5 x ULN (upper limit of normal)

- AST (SGOT) (aspartate aminotransferase), ALT (SGPT) (alanine
aminotransferase)and Alkaline Phosphatase ≤ 3 x ULN. If liver metastases
are present then ≤ 5 x ULN is allowed.

- Measured EDTA (ethylenediaminetetraacetic acid) renal clearance ≥ 45 mL/min
(within EU).

- Creatinine clearance ≥ 45 mL/min (within USA)

- Leucocytes > 2.5 x 109/ L

- Neutrophils > 1.0 x 109/L

- Platelets > 100 x 109/L

- Hemoglobin > 9.0 g/dL or > 5.6 mmol/l

- Acceptable coagulation status

- Negative pregnancy test/use of effective contraceptive methods for women of
childbearing potential.

- Serum potassium within normal range

Exclusion Criteria:

- More than three prior lines of chemotherapy given for metastatic disease

- History of a concurrent second malignancy

- History of hypersensitivity to either platinum or paclitaxel that cannot be
desensitized

- Co-existing active infection or any co-existing medical condition likely to interfere
with trial procedures, including:

- significant cardiovascular disease (New York Heart Association Class III or IV
cardiac disease)

- myocardial infarction within the past 6 months

- unstable angina

- congestive heart failure requiring therapy

- unstable arrhythmia or a need for anti-arrhythmic therapy

- evidence of ischemia on ECG

- marked baseline prolongation of QT/QTc ((corrected)QT interval) interval, e.g.,
repeated demonstration of a QTc interval > 500 msec;

- long QT Syndrome

- required use of concomitant medication on PXD101 infusion days that may cause
Torsade de Pointes.

- Bowel obstruction or impending bowel obstruction

- Known HIV positivity

- Mixed mullerian cancer of intra-uterine origin

- Any existing grade 2 or above drug-related neurotoxicity due to prior treatment with
agents causing neurotoxicity

- Altered mental status precluding understanding of the informed consent process and/or
completion of the necessary studies

- Treatment with investigational agents within the last 4 weeks

- Prior anticancer therapy within the last 3 weeks of trial dosing including
chemotherapy, radiotherapy, endocrine therapy or immunotherapy