A Study of 5 Fluorouracil and the Anti-Tumor Activity of ADH300004 and 5 Fluorouracil in Subjects With Incurable Solid Tumors

December 12, 2008 updated by: Adherex Technologies, Inc.

A 2-Part Phase 1 Study Evaluating the Safety and Anti-Tumor Activity of ADH300004 (Eniluracil) Administered With 5-Fluorouracil (5-FU), and the Pharmacokinetics of 5-FU Given as: 5.0 mg ADH300004 With Escalating Doses of 5-FU Administered Orally 3 Weeks Out of 4 in Subjects With Refractory Solid Tumors (Part 1); or 5.0 mg ADH300004 With 5 FU Administered Orally as a Split Dose for 3 Weeks Out of 4 in Subjects With Hepatocellular Carcinoma, Non-Small Cell Lung Carcinoma, Gastric Cancer, Cervical Cancer, Prostate Cancer, or Breast Cancer (Part 2) (Adherex Protocol Number AHX-03-104)

5 fluorouracil (5 FU), one of the most actively investigated anti-cancer drugs, is rapidly inactivated by the enzyme dihydropyrimidine dehydrogenase (DPD). ADH300004 blocks DPD. This study will test the safety and effects of oral ADH300004 14 hours prior to oral 5 FU in subjects with refractory solid tumors.

Study Overview

Status

Suspended

Conditions

Neoplasms

Intervention / Treatment

Drug: ADH300004

Study Type

Interventional

Enrollment (Anticipated)

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
- Tennessee
  - Nashville, Tennessee, United States, 37203
    - Sarah Cannon Research Institute

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

Genders Eligible for Study

All

Description

Inclusion Criteria:

Signed written informed consent
> or = 18 years of age
Advanced or metastatic solid tumors:

Part 1: Histologically proven advanced or metastatic solid tumors refractory to standard therapy or for which no standard therapy exists

Part 2: Histologically proven advanced and/or metastatic solid tumor of one of the following 6 histologies, that is refractory to standard curative therapy or for which no curative therapy exists: HCC, NSCLC, gastric cancer, cervical cancer, prostate cancer, and breast cancer

Radiologically documented measurable or evaluable (non-measurable) disease
Adequate performance status and organ function, as evidenced by hematologic and biochemical blood testing
Willing to not receive fluoropyrimidine containing chemotherapy for 8 weeks after the last dose of ADH300004 in this study

Exclusion Criteria:

Cytotoxic chemotherapy, radiotherapy, or investigational drug within 28 days prior to study entry
Non-cytotoxic cancer therapy within 14 days prior to study entry
Portal hypertension with bleeding esophageal or gastric varices within the past 3 months
Ascites that is refractory to conservative management
Inability to take oral medication
Active peptic ulcer disease
Known hypersensitivity to 5-FU or ADH300004
Stroke, major surgery, or other major tissue injury within 30 days before study entry

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: Non-Randomized
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: To determine the DLTs and MTD of the combination of ADH300004 and 5 FU administered orally in a weekly regimen, for 3 weeks with 1 week rest per cycle, in subjects with incurable solid tumors Time Frame: 4 weeks	4 weeks
Part 2: To determine the DLTs and MTD of the combination of ADH300004 and 5-FU administered orally as a split dose for 3 out of 4 weeks in subjects with HCC, NSCLC, gastric cancer, cervical cancer, prostate cancer, and breast cancer Time Frame: 4 weeks	4 weeks

Collaborators and Investigators

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

Sponsor

Adherex Technologies, Inc.

Investigators

Principal Investigator: Howard Burris, III, MD, SCRI Development Innovations, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Adherex Technologies Inc. Corporate Homepage

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

January 1, 2006

Primary Completion (Anticipated)

June 1, 2009

Study Registration Dates

First Submitted

December 12, 2005

First Submitted That Met QC Criteria