A Randomization Trial of Adjuvant Lamivudine/ Adefovir Dipivoxil Against Recurrence in Post-operative HBV-related Hepatocellular Carcinoma
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 117
- 试验地点
- 8
- 主要终点
- Primary endpoint: Primary endpoint: the 3-years recurrence rate (excluding those recur within first year).
研究概览
简要总结
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 copies/mL and ALT level > 2.0 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 cohort),in terms of the following endpoints.
- 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, i.e. 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.
详细描述
Treatment plan and Randomization scheme:
HBsAg+, HCC< 5 cm with curative resection Stratified with HBV DNA < 105 OR ≥ 105 copies/mL Genotype B or C RANDOMIZATION Prophylactic group Therapeutic control group Adefovir Dipivoxil 10mg/day x 36 months Lamivudine 100 mg/day x 18 months#, when HBV DNA =/> 105 copies/mL and ALT > 2.0 x UNL
- When YMDD mutant present, switch to Adefovir dipivoxil 10mg/day x 24 months. Selection of patients
- Eligibility Criteria (1)Histologically proven hepatocellular carcinoma. (2)HCC underwent curative resection within 6 weeks before registration. (3)Grossly, the resection margin should be > 1 cm. (4)Tumors, either single, < 5 cm in size or no more than 3 for size < 3 cm. (5)Patients must have a performance status of ECOG score < 2. (6)Patients must have adequate liver reservation and adequate hemogram. (i)Pugh-Child's Score < 7. (ii)The serum total bilirubin level are < 2 mg/dl. (iii)The prothrombin times are < 3 sec above normal control. (iv)The platelet are > 7.5 x 104 / mm3. (v)The WBC are > 3,000 / mm3. (7)Patient must have serum creatinine < 1.5 mg/dl (8)Cardiac function with NYHA classification < Grade II (9)HBsAg (+) . (10)Signed informed consent.
- Ineligibility Criteria
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven hepatocellular carcinoma.
- •HCC underwent curative resection within 6 weeks before registration.
- •Grossly, the resection margin should be > 1 cm.
- •Tumors, either single, < 5 cm in size or no more than 3 for size < 3 cm.
- •Patients must have a performance status of ECOG score <
- •Patients must have adequate liver reservation and adequate hemogram.
- •Pugh-Child's Score <
- •The serum total bilirubin level are < 2 mg/dl.
- •The prothrombin times are < 3 sec above normal control.
- •The platelet are > 7.5 x 104 / mm
- •The WBC are > 3,000 / mm
- •Patient must have serum creatinine < 1.5 mg/dl
- •Cardiac function with NYHA classification < Grade II
- •HBsAg (+) .
- •Signed informed consent.
排除标准
- •Patients who have non-curative resection are not eligible.
- •Resected HCCs with histologically positive margins are not eligible.
- •HCCs with radiological evidence of portal vein thrombus are not eligible.
- •Patients with other systemic diseases which required concurrent usage of glucoticosteroid or immunosuppressant agent(s) are not eligible.
- •Patients with advanced second primary malignancy are not eligible.
- •Patients with pregnancy or breast-feeding are not eligible.
- •Patients with severe cardiopulmonary diseases are not eligible.
- •Patients with clinically significant psychiatric disorder are not eligible.
- •Patients who had antineoplastic chemotherapeutic or immuno-therapeutic drugs or corticosteroids within 6 weeks of commencing the protocol are not eligible.
- •Patients who had prior lamividine and/or adefovir dipivoxil therapy are not eligible.
- •Anti-HCV positive patients are not eligible.
结局指标
主要结局
Primary endpoint: Primary endpoint: the 3-years recurrence rate (excluding those recur within first year).
时间窗: 6 years
次要结局
- Secondary endpoints: the first 2 year tumor recurrence rates,the recurrence-free survival,the overall survival.anti-viral efficacy.(7 years)