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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: ADH300004


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ADH300004|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Tumors, Neoplasms, Anticarcinogenic Agents, Antineoplastic Agents, Dihydrouracil Dehydrogenase (NADP)