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)”

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 Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment

Study Primary Completion Date: June 2009

Intervention(s) in this Clinical Trial

• Drug: ADH300004
  • 5 mg

Primary 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
    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
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Adherex Technologies, Inc.

Overall Clinical Trial Officials and Contacts

Howard Burris, III, MD Principal Investigator Sarah Cannon Research Institute  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00264472

Study ID Number: Adherex Protocol # AHX-03-104

ClinicalTrials.gov Identifier: NCT00264472

Health Authority: United States: Food and Drug Administration

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