Clinical trial NCT01640808: Study of Peretinoin for Suppressing Recurrence of HCV-positive HCC
Official title: NIK-333(Peretinoin) PhaseⅢ Study Investigation of the Efficacy and Safety to Suppress Recurrence of Hepatitis C Virus(HCV)-Positive Hepatocellular Carcinoma(HCC), Multicenter, Randomised, Double-blind, Placebo-controlled, Parallel-group Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatic Neoplasm Malignant Recurrent
Lead sponsor: Kowa Company, Ltd.
Sponsor class: INDUSTRY
First posted: 2012-07-16
Enrollment: 616
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to verify the superiority of NIK-333 (Peretinoin) to placebo in inhibiting the recurrence of HCV-positive HCC in patients showing complete cure of the disease, with the recurrence-free survival as the primary endpoint, in a multi-center, randomized, double-blind, placebo-controlled, parallel-group comparison study.


Eligibility criteria: Inclusion Criteria:

1. Patients with HCV-positive HCC who meet the following conditions before radical treatment

   * Patients diagnosed as having typical HCC on dynamic CT,CTA/CTAP, or dynamic MRI (nodule visualized as a high signal intensity area in the arterial phase and as a relatively low signal intensity area in the portal and equilibrium phases) performed within 8 weeks (56 days) before treatment start prior to radical therapy
   * Patients with the first primary HCC or the first recurrence of primary HCC
2. Patients who received the radical therapies. The treatment duration (from the start to the end of the treatment) should be within 4 weeks (28 days) for each of the radical therapies.
3. Patients showing a complete cure, as confirmed by the dynamic CT images taken from 8 weeks (56 days) to 12 weeks (84 days) after the end of the treatment show a non-stained low-concentration area overlapping the tumor image observed before complete cure.
4. Patients who are able to begin treatment with the study drug within 8 weeks (56 days) after dynamic CT to confirm complete cure
5. Patients confirmed of satisfying the following conditions based on the screening performed at subject registration

   * Positive for serum hepatitis C virus nucleic acid (HCV-RNA)
   * Grade A on Child-Pugh classification
   * Platelet count of 50 000/µL or higher
6. Patients with ECOG Performance Status score of 0 to 1
7. Patients of the age of 20 years or older at the time of informed consent

Exclusion Criteria:

1. Patients positive for HBs antigen
2. Patients showing vascular invasion of HCC on imaging diagnosis
3. Patients who have also undergone transcatheter arterial embolization therapy (TAE/TACE), transarterial infusion therapy (TAI), and chemolipiodolization in combination with the radical therapy
4. 4 Patients who want to receive antiviral therapy such as concomitant therapy with intaferon during the study period
5. Patients who have received other study drugs, anticancer drugs, or interferons after radical therapy
6. Patients who have hypertension as a complication, and whose blood pressure cannot be controlled by drug therapy (systolic blood pressure of 160 mmHg or higher or diastolic blood pressure of 100 mmHg or higher, as determined at subject registration)
7. Patients who have a history of allergy to CT contrast media, and whose participation in this study is judged to be inappropriate by the investigator or the subinvestigator
8. Patients with a history of total gastrectomy
9. Patients with a history of cardiac arrest
10. Patients with any of the following laboratory values or complications

    * Creatinine\>= 1.5mg/dL
    * Albumin urine \>= 1000mg/g Creatinine
    * Cardiac disorder corresponding to CTC-AE grade 3 in severity
    * HbA1c \>= 7.4 under treatment with insulin
    * Autoimmune disease or asthma being treated with oral steroid
11. Patients confirmed of having another malignant neoplasm or who had undergone a radical therapy of HCC within the past 5 years to treat another malignant neoplasm (however, this does not apply to endoscopic resection and resection of intraepithelial carcinoma)
12. Patients who are pregnant, who have a possibility of being pregnant or who have a desire to become pregnant during the study period
13. Lactating women
14. Patients who have a history of allergy to retinoid-related substances (vitamin A, etc.) in the past
15. Patients who participated in another clinical study within past 6 months

Primary outcomes:
measure: Recurrence-free Survival
timeFrame: Date of randomization to the date of recurrence of HCC (followed every 12 weeks) or death (whichever occurs first)
Secondary outcomes:
measure: Disease-free Survival
timeFrame: Date of randomization to the date of recurrence of HCC (followed every 12 weeks), death, or secondary cancer (malignant tumors other than HCC)(whichever occurs first)
measure: Time to Recurrence
timeFrame: Date of randomization to the date of recurrence of HCC(followed every 12 weeks)
Other outcomes:
Locations:
city: Nagoya
country: Japan
state: Aichi
city: Nagoya
country: Japan
state: Aichi
city: Kashiwa
country: Japan
state: Chiba
city: Matsuyama
country: Japan
state: Ehime
city: Iizuka
country: Japan
state: Fukuoka
city: Kurume
country: Japan
state: Fukuoka
city: Ogaki
country: Japan
state: Gifu
city: Sapporo
country: Japan
state: Hokkaido
city: Sapporo
country: Japan
state: Hokkaido
city: Sapporo
country: Japan
state: Hokkaido
city: Himeji
country: Japan
state: Hyogo
city: Kobe
country: Japan
state: Hyogo
city: Nishinomiya
country: Japan
state: Hyogo
city: Kanazawa
country: Japan
state: Ishikawa
city: Kawasaki
country: Japan
state: Kanagawa
city: Sagamihara
country: Japan
state: Kanagawa
city: Sagamihara
country: Japan
state: Kanagawa
city: Yokohama
country: Japan
state: Kanagawa
city: Yokohama
country: Japan
state: Kanagawa
city: Nankoku
country: Japan
state: Kochi
city: Kurashiki
country: Japan
state: Okayama
city: Ikeda
country: Japan
state: Osaka
city: Moriguchi
country: Japan
state: Osaka
city: Osakasayama
country: Japan
state: Osaka
city: Sakai
country: Japan
state: Osaka
city: Suita
country: Japan
state: Osaka
city: Iruma
country: Japan
state: Saitama
city: Sunto-gun
country: Japan
state: Shizuoka
city: Shimotsuke
country: Japan
state: Tochigi
city: Musashino
country: Japan
state: Tokyo,
city: Bunkyo-ku,
country: Japan
state: Tokyo
city: Bunkyo-ku
country: Japan
state: Tokyo
city: Bunkyo-ku
country: Japan
state: Tokyo
city: Chiyoda-ku
country: Japan
state: Tokyo
city: Chuo-ku
country: Japan
state: Tokyo
city: Minato-ku
country: Japan
state: Tokyo
city: Ota-ku
country: Japan
state: Tokyo
city: Setagaya-ku
country: Japan
state: Tokyo
city: Shibuya-ku
country: Japan
state: Tokyo
city: Shinjuku-ku
country: Japan
state: Tokyo
city: Shimonoseki
country: Japan
state: Yamaguchi
city: Ube
country: Japan
state: Yamaguchi
city: Kofu
country: Japan
state: Yamanashi
city: Chiba
country: Japan
city: Fukuoka
country: Japan
city: Fukuoka
country: Japan
city: Gifu
country: Japan
city: Gifu
country: Japan
city: Hiroshima
country: Japan
city: Hiroshima
country: Japan
city: Kagoshima
country: Japan
city: Kumamoto
country: Japan
city: Nagasaki
country: Japan
city: Niigata
country: Japan
city: Oita
country: Japan
city: Okayama
country: Japan
city: Osaka
country: Japan
city: Osaka
country: Japan
city: Osaka
country: Japan
city: Osaka
country: Japan
city: Osaka
country: Japan
city: Saga
country: Japan
city: Saga
country: Japan
city: Tokushima
country: Japan
city: Tokushima
country: Japan
city: Wakayama
country: Japan
Study officials:
References: