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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
TopoTarget A/S
ClinicalTrials.gov Identifier:
NCT00413322
First received: December 18, 2006
Last updated: November 29, 2013
Last verified: November 2013
  Purpose

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).


Condition Intervention Phase
Tumor
Drug: belinostat
Drug: 5-Fluorouracil (5-FU)
Phase 1

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

Resource links provided by NLM:


Further study details as provided by TopoTarget A/S:

Primary Outcome Measures:
  • to determine the maximum tolerated dose of PXD101 administered in combination with 5-FU [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]
  • to determine whether PXD101 alone can down-regulate thymidylate synthase in patient tumors [ Time Frame: throughout the study ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: September 2005
Study Completion Date: June 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single-arm dose escalation Drug: belinostat
300, 600, or 1000 mg/m2 belinostat IV for 5 days every 21 days starting with cycle 1
Other Name: PXD101
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.
Other Name: 5-FU

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00413322

Locations
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
United States, Nebraska
University of Nebraska
Omaha, Nebraska, United States, 68198-7680
United States, New Hampshire
Portsmouth Regional Hospital Hematology/Oncology Clinic
Portsmouth, New Hampshire, United States, 03801
Sponsors and Collaborators
TopoTarget A/S
  More Information

No publications provided

Responsible Party: TopoTarget A/S
ClinicalTrials.gov Identifier: NCT00413322     History of Changes
Other Study ID Numbers: PXD101-CLN-4
Study First Received: December 18, 2006
Last Updated: November 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by TopoTarget A/S:
Advanced Solid tumor
Adenosarcoma
Androgen-independent prostate cancer
belinostat
bladder cancer
bladder neoplasms
Breast cancer
Carcinoma, Bronchogenic
Carcinoma, Non-Small-Cell Lung
Carcinoma, Small Cell
Carcinosarcoma
Chondrosarcoma
Coin Lesion, Pulmonary
colorectal cancer
Esophageal Neoplasms
Facial Neoplasms
Fibrosarcoma
head and neck cancer
Hemangiosarcoma
Histiocytoma, Malignant Fibrous
kidney cancer
Leiomyosarcoma
Liposarcoma
lung cancer
lung neoplasms
Lymphangiosarcoma
mesothelioma
mesothelioma, cystic
Mixed Tumor, Mesodermal
Mouth Neoplasms

Additional relevant MeSH terms:
Neoplasms
Fluorouracil
Belinostat
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Histone Deacetylase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014