Ignite Creation Date:
2024-05-05 @ 5:25 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00455091
Status:
TERMINATED
Last Update Posted:
2017-04-28
First Post:
2007-04-02
Brief Title:
A Phase III Study in Post-operative HBV-related Hepatocellular Carcinoma
Sponsor:
National Health Research Institutes Taiwan
Organization:
National Health Research Institutes Taiwan
Study Overview
Official Title:
A Randomization Trial of Adjuvant Lamivudine Adefovir Dipivoxil Against Recurrence in Post-operative HBV-related Hepatocellular Carcinoma
Status:
TERMINATED
Status Verified Date:
2009-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
No cases enrollment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Research Objective and Study End Points To evaluate the anti-HBV as well as HCC recurrence reducing effects of standard 18 months lamivudine treatment at time of HBV reactivation with hepatitis flare up HBV DNA 105 copiesmL and ALT level 20 x UNL or prophylactic prolong 36 months adefovir dipivoxil therapy in post-operative HBsAg 5 cm HCC patients and to compare the results of who group with historical controls T1297 HBsAg 5 cm HCC cohortin terms of the following endpoints
1 Primary endpoint
the 3-years recurrence rate excluding those recur within first year
2 Secondary endpoints
the first 2 year tumor recurrence rates the recurrence-free survival the overall survival anti-viral efficacy ie biochemical response and viral response rate to correlate the changes of viral titer with the clinical outcome in post- operative HCC patients with adjuvant lamivudine or adefovir therapy
1 Primary endpoint
the 3-years recurrence rate excluding those recur within first year
2 Secondary endpoints
the first 2 year tumor recurrence rates the recurrence-free survival the overall survival anti-viral efficacy ie biochemical response and viral response rate to correlate the changes of viral titer with the clinical outcome in post- operative HCC patients with adjuvant lamivudine or adefovir therapy
Detailed Description:
Treatment plan and Randomization scheme
HBsAg HCC 5 cm with curative resection Stratified with HBV DNA 105 OR 105 copiesmL Genotype B or C RANDOMIZATION Prophylactic group Therapeutic control group Adefovir Dipivoxil 10mgday x 36 months Lamivudine 100 mgday x 18 months when HBV DNA 105 copiesmL and ALT 20 x UNL
When YMDD mutant present switch to Adefovir dipivoxil 10mgday x 24 months Selection of patients
1 Eligibility Criteria 1Histologically proven hepatocellular carcinoma 2HCC underwent curative resection within 6 weeks before registration 3Grossly the resection margin should be 1 cm 4Tumors either single 5 cm in size or no more than 3 for size 3 cm 5Patients must have a performance status of ECOG score 2 6Patients must have adequate liver reservation and adequate hemogram iPugh-Childs Score 7 iiThe serum total bilirubin level are 2 mgdl iiiThe prothrombin times are 3 sec above normal control ivThe platelet are 75 x 104 mm3 vThe WBC are 3000 mm3 7Patient must have serum creatinine 15 mgdl 8Cardiac function with NYHA classification Grade II 9HBsAg 10Signed informed consent
2 Ineligibility Criteria
-- --
1 Patients who have non-curative resection are not eligible
2 Resected HCCs with histologically positive margins are not eligible
3 HCCs with radiological evidence of portal vein thrombus are not eligible
4 Patients with other systemic diseases which required concurrent usage of glucoticosteroid or immunosuppressant agents are not eligible
5 Patients with advanced second primary malignancy are not eligible
6 Patients with pregnancy or breast-feeding are not eligible
7 Patients with severe cardiopulmonary diseases are not eligible
8 Patients with clinically significant psychiatric disorder are not eligible
9 Patients who had antineoplastic chemotherapeutic or immuno-therapeutic drugs or corticosteroids within 6 weeks of commencing the protocol are not eligible
10 Patients who had prior lamividine andor adefovir dipivoxil therapy are not eligible
11 Anti-HCV positive patients are not eligible Statistical Consideration
Sample size
With a phase III superior study design to give an 80 power with a two-sided 5 significance level 139 patients per each treatment arm should be included in the study If a 10 drop-out rate is included totally 309 patients 155 per study arm will be required
Analysis
The objectives are as follows
1Primary endpoint the 3-year recurrence rate excluding those recur within 1st year
1 Second endpoints the recurrence-free survival
2 Second endpoints the overall survival
3 Second endpoints anti-viral efficacy in terms of sustained biochemical response rate and viral response rate To correlate the changes of viral titer with the clinical outcome 2 RFS and OS are computed from the date of randomization
1 In analysis of RFS patients died without disease recurrence will be censored for recurrence at the date of death 2 In analysis of OS an event is defined as death from any cause 3 The survival distributions of RFS and OS will be estimated by the Kaplan and Meier method
4 Statistical comparisons of RFS and OS between the two treatment arms will be performed with the log-rank test
5 Cox proportional hazards model will be used to assess the importance of potential prognostic factors as well as to test the significance of treatment when adjusting for factors 39
3Tumor size Liver inflammation viral status ie HBV genotype and DNA titer
HBsAg HCC 5 cm with curative resection Stratified with HBV DNA 105 OR 105 copiesmL Genotype B or C RANDOMIZATION Prophylactic group Therapeutic control group Adefovir Dipivoxil 10mgday x 36 months Lamivudine 100 mgday x 18 months when HBV DNA 105 copiesmL and ALT 20 x UNL
When YMDD mutant present switch to Adefovir dipivoxil 10mgday x 24 months Selection of patients
1 Eligibility Criteria 1Histologically proven hepatocellular carcinoma 2HCC underwent curative resection within 6 weeks before registration 3Grossly the resection margin should be 1 cm 4Tumors either single 5 cm in size or no more than 3 for size 3 cm 5Patients must have a performance status of ECOG score 2 6Patients must have adequate liver reservation and adequate hemogram iPugh-Childs Score 7 iiThe serum total bilirubin level are 2 mgdl iiiThe prothrombin times are 3 sec above normal control ivThe platelet are 75 x 104 mm3 vThe WBC are 3000 mm3 7Patient must have serum creatinine 15 mgdl 8Cardiac function with NYHA classification Grade II 9HBsAg 10Signed informed consent
2 Ineligibility Criteria
-- --
1 Patients who have non-curative resection are not eligible
2 Resected HCCs with histologically positive margins are not eligible
3 HCCs with radiological evidence of portal vein thrombus are not eligible
4 Patients with other systemic diseases which required concurrent usage of glucoticosteroid or immunosuppressant agents are not eligible
5 Patients with advanced second primary malignancy are not eligible
6 Patients with pregnancy or breast-feeding are not eligible
7 Patients with severe cardiopulmonary diseases are not eligible
8 Patients with clinically significant psychiatric disorder are not eligible
9 Patients who had antineoplastic chemotherapeutic or immuno-therapeutic drugs or corticosteroids within 6 weeks of commencing the protocol are not eligible
10 Patients who had prior lamividine andor adefovir dipivoxil therapy are not eligible
11 Anti-HCV positive patients are not eligible Statistical Consideration
Sample size
With a phase III superior study design to give an 80 power with a two-sided 5 significance level 139 patients per each treatment arm should be included in the study If a 10 drop-out rate is included totally 309 patients 155 per study arm will be required
Analysis
The objectives are as follows
1Primary endpoint the 3-year recurrence rate excluding those recur within 1st year
1 Second endpoints the recurrence-free survival
2 Second endpoints the overall survival
3 Second endpoints anti-viral efficacy in terms of sustained biochemical response rate and viral response rate To correlate the changes of viral titer with the clinical outcome 2 RFS and OS are computed from the date of randomization
1 In analysis of RFS patients died without disease recurrence will be censored for recurrence at the date of death 2 In analysis of OS an event is defined as death from any cause 3 The survival distributions of RFS and OS will be estimated by the Kaplan and Meier method
4 Statistical comparisons of RFS and OS between the two treatment arms will be performed with the log-rank test
5 Cox proportional hazards model will be used to assess the importance of potential prognostic factors as well as to test the significance of treatment when adjusting for factors 39
3Tumor size Liver inflammation viral status ie HBV genotype and DNA titer
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None