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

• Sponsor: Eisai Limited (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00165633
• Collaborator: (none)
• Enrollment: 540
• Locations: 30
• Arms: 3
• Duration (Months): 36
• Patients Per Site: 18
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Menatetrenone; Drug: Menatetrenone; Drug: Placebo	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 540 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-Controlled, Phase II/III Clinical Study on Inhibitory Effects of E0167 on Recurrence of Hepatocellular Carcinoma
• Study Start Date: Mar 1, 2004
• Actual Study Completion Date: Mar 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Menatetrenone; 45 mg capsule, orally, three times a day, after meals.; Other Names: E0167
Experimental: 2	Drug: Menatetrenone; 90 mg capsule, orally, three times a day, after meals.; Other Names: E0167
Placebo Comparator: 3	Drug: Placebo; Placebo capsule, orally, three times a day, after meals.

Outcome Measures

Primary Outcome Measures

1. Relapse-free survival period. [Every 3 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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
• 1. Patients who underwent tumor biopsy and are histopathologically diagnosed as hepatocellular carcinoma

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

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

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

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

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

1. 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

1. Systemic conditions:

• 1. Patients unable to receive oral administration
• 1. Patients with a history of gastrectomy or extensive resection of digestive tract
• 1. Patients who are suspected to have biliary occlusion, choleretic disorder, cholecystectomy, or malabsorption of liposoluble agents
• 1. 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)
• 1. 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])

1. Drug administration:

• 1. Patients on warfarin potassium therapy
• 1. Patients with a known history of drug allergy to E0167 or its ingredients
• 1. 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. Other exclusion criteria

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Fukuoka	Fukuoka-prefecture	Japan	814-0133
2		Kurume	Fukuoka-prefecture	Japan	830-0011
3		Naka	Hiroshima-prefecture	Japan	730-001
4		Sapporo	Hokkaido-prefecture	Japan	006-8111
5		Sapporo	Hokkaido-prefecture	Japan	060-0033
6		Hitachi	Ibaraki-prefecture	Japan	317-0077
7		Morioka	Iwate-prefecture	Japan	020-0023
8		Kawasaki	Kanagawa-prefecture	Japan	213-0001
9		Kanazawa	Kanazawa-prefecture	Japan	920-0934
10		Senndai	Miyagi-prefecture	Japan	980-0872
11		Niigata	Niigata-prefecture	Japan	951-8122
12		Oita	Oita-prefecture	Japan	879-5503
13		Kurashiki	Okayama-prefecture	Japan	710-0052
14		Okayama	Okayama-prefecture	Japan	700-0013
15		Okayama	Okayama-prefecture	Japan	700-0014
16		Moriguchi	Osaka-prefecture	Japan	570-0074
17		Osakasayama	Osaka-prefecture	Japan	589-0014
18		Osaka	Osaka-prefecture	Japan	537-0025
19		Osaka	Osaka-prefecture	Japan	543-0021
20		Osaka	Osaka-prefecture	Japan	543-0027
21		Saga	Saga-prefecture	Japan	840-0054
22		Saga	Saga-prefecture	Japan	849-0937
23		Shizuoka	Shizuoka-prefecture	Japan	420-0881
24		Bunkyo-ku	Tokyo	Japan	113-0033
25		Chiyoda-ku	Tokyo	Japan	101-0024
26		Setagaya-ku	Tokyo	Japan	158-0098
27		Shibuya-ku	Tokyo	Japan	151-0053
28		Shinjuku-ku	Tokyo	Japan	162-0052
29		Wakayama	Wakayama-prefecture	Japan	641-0012
30		Ube	Yamaguchi-prefecture	Japan	755-0046

Sponsors and Collaborators

• Eisai Limited

Investigators

• Study Director: Nozomu Koyanagi, Eisai Co., Ltd - Development Clinical Research Department. Clinical Research Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00165633
• Other Study ID Numbers: E0167-J081-551
• First Posted: Sep 14, 2005
• Last Update Posted: Dec 9, 2008
• Last Verified: Dec 1, 2008

• Keywords provided by , ,: Hepatocellular; Carcinoma; Hepatitis C Virus; Hepatitis B Virus; recurrence; Vitamin K2; E0167
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Recurrence; Vitamin K 2; Menatetrenone

Study Results

No Results Posted as of Dec 9, 2008