Clinical trial NCT00319683: A Study of ADH300004 and 5-Fluorouracil in Locally Advanced, Recurrent, or Metastatic Hepatocellular Carcinoma
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Cancer
Tumors
Neoplasms
Anticarcinogenic Agents
Antineoplastic Agents
Dihydrouracil Dehydrogenase (NADP)
Lead sponsor: Adherex Technologies, Inc.
Sponsor class: INDUSTRY
First posted: 2006-04-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Honolulu
country: United States
facility: Queens Medical Center
state: Hawaii
city: Singapore
country: Singapore
facility: Johns Hopkins Singapore International Medical Center
city: Chiayi
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Chung-Ho Memorial Hospital, Kaohsiung Medical University
city: Taipei
country: Taiwan
facility: National Health Research Institute, Ward Veterans General Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
Study officials:
affiliation: National Health Research Institute, Ward Veterans General Hospital
name: Jacqueline Whang-Peng, MD
role: PRINCIPAL_INVESTIGATOR
References: