A Phase II/III Clinical Study on Inhibitory Effects of E0167 on Recurrence of Hepatocellular Carcinoma

NCT ID: NCT00165633

Last Updated: 2008-12-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 540 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31
• Study Completion Date: 2007-03-31

Brief Summary

The purpose of this study is to determine the superiority of inhibitory effects and safety of Menatetrenone (E0167) on recurrence in patients with hepatocellular carcinoma.

Detailed Description

The study was conducted as a multicenter, randomized, parallel, placebo-controlled, double-blind comparative clinical study. Patients were randomly assigned in a double-blind manner to receive 45 or 90 mg/day of oral vitamin K2 or an identical-appearing placebo. Study drug was administered orally three times daily after meals until recurrence.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular; Carcinoma; Hepatitis C Virus; Hepatitis B Virus; recurrence; Vitamin K2; E0167

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

Group Type: EXPERIMENTAL

Menatetrenone

Intervention Type: DRUG

45 mg capsule, orally, three times a day, after meals.

2

Group Type: EXPERIMENTAL

Menatetrenone

Intervention Type: DRUG

90 mg capsule, orally, three times a day, after meals.

3

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsule, orally, three times a day, after meals.

Interventions

Menatetrenone

45 mg capsule, orally, three times a day, after meals.

Intervention Type: DRUG

Menatetrenone

90 mg capsule, orally, three times a day, after meals.

Intervention Type: DRUG

Placebo

Placebo capsule, orally, three times a day, after meals.

Intervention Type: DRUG

Other Intervention Names

E0167; E0167

Eligibility Criteria

Inclusion Criteria

1. 20 years or older at the time of obtaining consent.

2. Systemic conditions are 0 to 2 score of Performance Status (according to Eastern Cooperative Oncology Group: ECOG).

3. Diagnosis of hepatocellular carcinoma is based on the following 1) or 2).

• 1) Patients who are confirmed to have early tumor stain and typical finding(s) of hepatocellular carcinoma with CT or MRI imaging
• 2) Patients who underwent tumor biopsy and are histopathologically diagnosed as hepatocellular carcinoma

4. Primary onset or recurrence of hepatocellular carcinoma is not more than 1 time.

5. Patients who underwent the following 1) or 2) within 90 days prior to registration to determine therapeutic effect.

• 1) Patients who underwent local therapy to achieve complete hepatonecrosis and are confirmed to have complete hepatonecrosis with CT imaging or MRI.
• 2) Patients who underwent surgical treatment(s) and are confirmed not to have residual tumor with CT or MRI imaging.

6. Patients who meet the following items to determine liver function:

• 1) Albumin is 2.8 g/dL or above
• 2) Total bilirubin is under 2.0 mg/dL
• 3) Prothrombin activation is 40% or above

7. Patients who are given full explanation of study participation (including cancer notification) and submit written consent forms with their understanding as well as voluntary will for this study.

Exclusion Criteria

1. Hepatocellular carcinoma:

• 1) Patients who have extrahepatic metastasis
• 2) Patients who have portal invasion
• 3) Patients who experienced with systemic administration of anti-malignant tumor drugs to treat hepatocellular carcinoma
• 4) Patients treated with transcatheter arterial chemoembolization (TAE) alone as a non-local therapy for hepatocellular carcinoma

2. Hepatitis:

-- 1) Patients of (a) or (b) previously treated with interferon preparations (including clinical studies).

• (a) Patients with chronic hepatitis C virus (HCV) showing HCV-RNA negative
• (b) Patients with viral hepatitis treated with interferon preparations within the last 2 years (from the same day, 6 months earlier to the day of obtaining consent forms)
• (c) Patients with encephalopathy in which pharmacotherapy is ineffective
• (d) Patients with ascites or pleural effusion that cannot be managed with diuretics

3. Systemic conditions:

• 1) Patients unable to receive oral administration
• 2) Patients with a history of gastrectomy or extensive resection of digestive tract
• 3) Patients who are suspected to have biliary occlusion, choleretic disorder, cholecystectomy, or malabsorption of liposoluble agents
• 4) Patients with complicated serious diseases such as cardiovascular (e.g., myocardial infarction), hematological (e.g., aplastic anemia), and/or renal dysfunctions (e.g., acute and chronic renal failure)
• 5) Patients with multiple cancers (within a 5-year cancer-free period [from the same day of 5 years earlier to the day of obtaining consent forms])

4. Drug administration:

• 1) Patients on warfarin potassium therapy
• 2) Patients with a known history of drug allergy to E0167 or its ingredients
• 3) Patients who received vitamin K preparations within the recent 6 months (from the same day of 6 month earlier to the day of obtaining consent forms)

• 1) Women of pregnant, lactating, childbearing potential, or with the intention of becoming pregnant
• 2) Patients who are presently participating in another clinical study (except for follow-up surveys for study outcomes)
• 3) Patients who are judged to be ineligible for study entry by the investigator or subinvestigator

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Eisai Company Limited

Principal Investigators

Nozomu Koyanagi

Role: STUDY_DIRECTOR

Eisai Co., Ltd - Development Clinical Research Department. Clinical Research Center

Locations

Fukuoka, Fukuoka, Japan

Kurume, Fukuoka, Japan

Naka, Hiroshima, Japan

Sapporo, Hokkaido-prefecture, Japan

Sapporo, Hokkaido-prefecture, Japan

Hitachi, Ibaraki, Japan

Morioka, Iwate, Japan

Kawasaki, Kanagawa, Japan

Kanazawa, Kanazawa-prefecture, Japan

Senndai, Miyagi, Japan

Niigata, Niigata, Japan

Ōita, Oita Prefecture, Japan

Kurashiki, Okayama-ken, Japan

Okayama, Okayama-ken, Japan

Okayama, Okayama-ken, Japan

Moriguchi, Osaka, Japan

Osaka, Osaka, Japan

Osaka, Osaka, Japan

Osaka, Osaka, Japan

Sayama, Osaka, Japan

Saga, Saga-ken, Japan

Saga, Saga-ken, Japan

Shizuoka, Shizuoka, Japan

Bunkyo-ku, Tokyo, Japan

Chiyoda-ku, Tokyo, Japan

Setagaya-ku, Tokyo, Japan

Shibuya-ku, Tokyo, Japan

Shinjuku-ku, Tokyo, Japan

Wakayama, Wakayama, Japan

Ube, Yamaguchi, Japan

Countries

Japan

Other Identifiers

E0167-J081-551

Identifier Type: -

Identifier Source: org_study_id