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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00165633
Recruitment Status : Terminated
First Posted : September 14, 2005
Last Update Posted : December 9, 2008
Information provided by:
Eisai Inc.

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: 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : March 2004
Actual Study Completion Date : March 2007

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1 Drug: Menatetrenone
45 mg capsule, orally, three times a day, after meals.
Other Name: E0167

Experimental: 2 Drug: Menatetrenone
90 mg capsule, orally, three times a day, after meals.
Other Name: E0167

Placebo Comparator: 3 Drug: Placebo
Placebo capsule, orally, three times a day, after meals.

Primary Outcome Measures :
  1. Relapse-free survival period. [ Time Frame: Every 3 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
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
    • 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)
  5. Other exclusion criteria

    • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00165633

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Fukuoka, Fukuoka-prefecture, Japan, 814-0133
Kurume, Fukuoka-prefecture, Japan, 830-0011
Naka, Hiroshima-prefecture, Japan, 730-001
Sapporo, Hokkaido-prefecture, Japan, 006-8111
Sapporo, Hokkaido-prefecture, Japan, 060-0033
Hitachi, Ibaraki-prefecture, Japan, 317-0077
Morioka, Iwate-prefecture, Japan, 020-0023
Kawasaki, Kanagawa-prefecture, Japan, 213-0001
Kanazawa, Kanazawa-prefecture, Japan, 920-0934
Senndai, Miyagi-prefecture, Japan, 980-0872
Niigata, Niigata-prefecture, Japan, 951-8122
Oita, Oita-prefecture, Japan, 879-5503
Kurashiki, Okayama-prefecture, Japan, 710-0052
Okayama, Okayama-prefecture, Japan, 700-0013
Okayama, Okayama-prefecture, Japan, 700-0014
Moriguchi, Osaka-prefecture, Japan, 570-0074
Osakasayama, Osaka-prefecture, Japan, 589-0014
Osaka, Osaka-prefecture, Japan, 537-0025
Osaka, Osaka-prefecture, Japan, 543-0021
Osaka, Osaka-prefecture, Japan, 543-0027
Saga, Saga-prefecture, Japan, 840-0054
Saga, Saga-prefecture, Japan, 849-0937
Shizuoka, Shizuoka-prefecture, Japan, 420-0881
Bunkyo-ku, Tokyo, Japan, 113-0033
Chiyoda-ku, Tokyo, Japan, 101-0024
Setagaya-ku, Tokyo, Japan, 158-0098
Shibuya-ku, Tokyo, Japan, 151-0053
Shinjuku-ku, Tokyo, Japan, 162-0052
Wakayama, Wakayama-prefecture, Japan, 641-0012
Ube, Yamaguchi-prefecture, Japan, 755-0046
Sponsors and Collaborators
Eisai Limited
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Study Director: Nozomu Koyanagi Eisai Co., Ltd - Development Clinical Research Department. Clinical Research Center
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Responsible Party: Customer Information Services Department. CRC and QA, Eisai Company Limited Identifier: NCT00165633    
Other Study ID Numbers: E0167-J081-551
First Posted: September 14, 2005    Key Record Dates
Last Update Posted: December 9, 2008
Last Verified: December 2008
Keywords provided by Eisai Inc.:
Hepatitis C Virus
Hepatitis B Virus
Vitamin K2
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Disease Attributes
Pathologic Processes
Vitamin K 2
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Growth Substances
Physiological Effects of Drugs