Study of PXD101 Alone and in Combination With 5-Fluorouracil (5-FU) 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