A Study of ADH300004 and 5-Fluorouracil in Locally Advanced, Recurrent, or Metastatic Hepatocellular Carcinoma

A Phase 1/2 Study in Subjects With Locally Advanced, Recurrent, or Metastatic Hepatocellular Carcinoma, Evaluating the Safety, and Anti-Tumor Activity of ADH300004 (Eniluracil) With Escalating Doses of 5 Fluorouracil Administered Orally Once Weekly for 3 Weeks Out of Every 4 (Adherex Protocol Number AHX-03-103)

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 locally advanced, recurrent, or metastatic hepatocellular carcinoma.

Inclusion Criteria:

• Signed written informed consent
• In the Phase I portion, Asian subjects that are > or = to 18 years of age
• In the Phase II portion, any subjects that are > or = to 18 years of age
• Non-resectable locally advanced, recurrent, or metastatic hepatocellular carcinoma (HCC) that is either histologically proven or a radiologically documented liver mass with: (alpha-fetoprotein [AFP] > 4,000 ng/mL, hepatitis B surface antigen positive or alpha-fetoprotein [AFP] > 400 ng/mL, hepatitis B surface antigen negative)
• Radiologically documented 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:

• Chemotherapy, radiotherapy, or any other investigational drug within 28 days prior to study entry
• No more than 1 previous treatment with systemic chemotherapy (chemotherapy administered as part of a chemo-embolization procedure is not considered systemic chemotherapy)
• 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
• History of primary brain tumors or brain metastases
• Previous or concurrent malignancy at another site within the last 5 years
• Stroke, major surgery, or other major tissue injury within 30 days before study entry