Official Title: “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).

Study Type: Interventional

Study Design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: March 2008

Intervention(s) in this Clinical Trial

• Drug: belinostat
  • 300, 600, or 1000 mg/m2 belinostat IV for 5 days every 21 days starting with cycle 1
• Drug: 5-Fluorouracil (5-FU)
  • 250, 500, 750, or 1000 mg/m2/d of 5-FU starting with cycle 2 onwards in combination with belinostat. Starting on day 2, 5-FU is administered as a continuous 96 hour infusion.

Primary Measures

• to determine the maximum tolerated dose of PXD101 administered in combination with 5-FU
  • Time Frame: throughout the study
    Safety Issue?: Yes
• to determine whether PXD101 alone can down-regulate thymidylate synthase in patient tumors
  • Time Frame: throughout the study
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: TopoTarget A/S

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00413322

Study ID Number: PXD101-CLN-4

ClinicalTrials.gov Identifier: NCT00413322

Health Authority: United States: Food and Drug Administration