Study of PXD101 Alone and in Combination With 5-Fluorouracil (5-FU) in Patients With Advanced Solid Tumors

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

This is a study to assess the combination of PXD101 and 5-Fluorouracil (5-FU)in patients with advanced solid tumors. The primary goal of the study is to understand the safety, anti-tumor activity, and how the study drug behaves within the body when given with 5-Fluorouracil (5-FU).

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