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

Sponsor:	Adherex Technologies, Inc.
Information provided by:	Adherex Technologies, Inc.
ClinicalTrials.gov Identifier:	NCT00264472

Purpose

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.

Condition	Intervention	Phase
Neoplasms	Drug: ADH300004	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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)

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Cancer Cervical Cancer Prostate Cancer Stomach Cancer

Drug Information available for: Fluorouracil 5-Ethynyluracil

U.S. FDA Resources

Further study details as provided by Adherex Technologies, Inc.:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	January 2006
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Intervention Details:

5 mg

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00264472

Locations

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

Sponsors and Collaborators

Adherex Technologies, Inc.

Investigators

Principal Investigator:

Howard Burris, III, MD

Sarah Cannon Research Institute

More Information

Additional Information:

Adherex Technologies Inc. Corporate Homepage This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Clinical Study Manager, Adherex Technoloogies
ClinicalTrials.gov Identifier:	NCT00264472 History of Changes
Other Study ID Numbers:	Adherex Protocol # AHX-03-104
Study First Received:	December 12, 2005
Last Updated:	December 12, 2008
Health Authority:	United States: Food and Drug Administration

Keywords provided by Adherex Technologies, Inc.:

Cancer
Tumors
Neoplasms

Anticarcinogenic Agents
Antineoplastic Agents
Dihydrouracil Dehydrogenase (NADP)

Additional relevant MeSH terms:

Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Hepatocellular
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

Liver Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Fluorouracil
Dihydrouracil Dehydrogenase (NADP)
Anticarcinogenic Agents
5-ethynyluracil
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents

ClinicalTrials.gov processed this record on February 12, 2012