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

Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00413322
• Other study ID #: PXD101-CLN-4
• Status: Completed
• Phase: Phase 1
• First received: December 18, 2006
• Last updated: July 7, 2015
• Start date: September 2005
• Est. completion date: June 2008

Study information

• Verified date: July 2015
• Source: Onxeo
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: June 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tumor

Intervention

Drug:
• belinostat
300, 600, or 1000 mg/m2 belinostat IV for 5 days every 21 days starting with cycle 1
• 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.

Locations

Country	Name	City	State
United States	University of Nebraska	Omaha	Nebraska
United States	Portsmouth Regional Hospital Hematology/Oncology Clinic	Portsmouth	New Hampshire
United States	Mayo Clinic Arizona	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Onxeo

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	to determine the maximum tolerated dose of PXD101 administered in combination with 5-FU		throughout the study	Yes
Primary	to determine whether PXD101 alone can down-regulate thymidylate synthase in patient tumors		throughout the study	No