A Phase I Safety, Pharmacodynamic, Anti-Tumor Activity, and Pharmacokinetic Study of PXD101 Alone and in Combination With 5-Fluorouracil in Patients With Advanced Solid Tumors

Inclusion Criteria:

- Histologically confirmed solid tumors

- Advanced colorectal cancer or other adenocarcinomas

- Tumor progression after standard chemotherapy, or where none yet approved

- At least one unidimensionally measurable lesion

- Karnofsky performance >= 70%

- Life expectancy of at least 3 months

- Age >= 18 years

- Signed, written Institutional Review Board (IRB)-approved informed consent

- Acceptable liver function:

- Bilirubin <= 1.5 x upper limit of normal (ULN)

- AST (SGOT) and ALT (SGPT) <= 2.5 x ULN, OR

- AST (SGOT) and ALT (SGPT) <= 5 x ULN if liver metastasis

- Acceptable renal function:

- Serum creatinine within normal limits, OR

- Calculated creatinine clearance of >= 60 mL/min/1.73 m2 for certain patients

- Acceptable hematologic status:

- Absolute neutrophil count (ANC) >= 1500 cells/mm3

- Platelet count >= 100,000 (plt/mm3)

- Hemoglobin >= 9 g/dL

- Urinalysis: No clinically significant abnormalities

- Acceptable coagulation status:

- Prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits, OR

- For patients on anticoagulation therapy, status within therapeutic range

- For men and women of child-producing potential, use of effective contraception

- Tumors accessible for needle biopsy

Exclusion Criteria:

- Significant cardiovascular disease.

- A marked baseline prolongation of QT/QTc interval

- Long QT syndrome

- Required use of medication on dosing days that may cause torsade de pointes.

- Infections requiring intravenous (IV) systemic therapy

- Pregnant or nursing women

- Treatment with chemotherapy or investigational therapy < 4 weeks (28 days) prior to
study entry (6 weeks for nitrosoureas, mitomycin C, or Avastin).

- Treatment with radiation therapy or surgery either within 2 weeks prior to study
entry, or not yet recovered if 2-4 weeks prior to study entry.

- Unwillingness or inability to comply with protocol procedures.

- Known active uncontrolled infection with HIV, hepatitis B, or hepatitis C

- Serious nonmalignant disease (e.g. hydronephrosis, liver failure, or other
conditions) that could compromise protocol objectives in the opinion of the
investigator and/or the sponsor

- Concurrent use of other investigational agent(s)

- Serious concurrent medical illness