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

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 refractory solid tumors.

Official Title
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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)

Conditions
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Neoplasms

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 > 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

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|5 mg|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | 4 weeks | 
| 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 |  | 4 weeks | 

 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)