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

July 7, 2015 updated by: Onxeo

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic Arizona
    • Nebraska
      • Omaha, Nebraska, United States, 68198-7680
        • University of Nebraska
    • New Hampshire
      • Portsmouth, New Hampshire, United States, 03801
        • Portsmouth Regional Hospital Hematology/Oncology Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
to determine the maximum tolerated dose of PXD101 administered in combination with 5-FU
Time Frame: throughout the study
throughout the study
to determine whether PXD101 alone can down-regulate thymidylate synthase in patient tumors
Time Frame: throughout the study
throughout the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Onxeo

Investigators

  • Study Chair: Topotarget A/S, Onxeo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

June 1, 2008

Study Registration Dates

First Submitted

December 18, 2006

First Submitted That Met QC Criteria

December 18, 2006

First Posted (Estimate)

December 19, 2006

Study Record Updates

Last Update Posted (Estimate)

July 8, 2015

Last Update Submitted That Met QC Criteria

July 7, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PXD101-CLN-4

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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