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

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.

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