Hepatocellular CarcinomaPhase 3NCT00149565
Phase Ⅲ Randomized Trial in Postoperative Hepatocellular Carcinoma
A Phase 3 study testing IFN-α2b in people with Hepatocellular Carcinoma, run by National Health Research Institutes, Taiwan at 1 site in Taiwan.
Trial summary
OBJECTIVES 1. To investigate whether adjuvant IFN-α therapy can delay or reduce the 2-5 years recurrence rate in curatively resected HCC . 2. To examine whether adjuvant IFN-α therapy can prolong the disease-free survival in curatively resected HCC. 3. Read more about this study
- Who is it for?
- Ages 20 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- IFN-α2b
- How many people
- 268 participants
- Where
- 1 siteTaiwan
- Study dates
- Oct 1997to Jul 2005
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Histologically proven hepatocellular carcinoma.
- HCC underwent curative resection within 6 weeks before registration.
- Grossly, the resection margin should be > 1 cm.
- Patients must be younger than 70 year-old.
- Patients must have a performance status of ECOG score < 2.
- Patients must have adequate liver reservation and adequate hemogram.
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- Pugh-Child's Score < 7.
- The serum total bilirubin level are < 2 mg/dl.
- The prothrombin times are < 3 sec above normal control.
- The platelet are > 10 x 104 / mm3.
- The WBC are > 3,000 / mm3.
- Patient must have serum creatinine < 1.5 mg/dl
- Cardiac function with NYHA classification < Grade II
- Known HBV or HCV status.
- Signed informed consent.
Who cannot join
- 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 glucocorticosteroid or immunosuppressant agent(s) are not eligible.
- Patients with advanced second primary malignancy are not eligible.
- Patients with pregnacy or breast-feeding are not eligible.
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hepatocellular Carcinoma Postoperative Adjuvant Therapy Disease Committee of Taiwan Cooperative Oncology Group
- OBJECTIVES
- To investigate whether adjuvant IFN-α therapy can delay or reduce the 2-5 years recurrence rate in curatively resected HCC .
- To examine whether adjuvant IFN-α therapy can prolong the disease-free survival in curatively resected HCC.
- To determine the safety and tolerance of adjuvant IFN-α therapy in postoperative HCC with or without cirrhosis.
- To investigate the change of activity of HBV and HCV in postoperative HCC patients with adjuvant IFN-α therapy.
- To correlate the changes of viral status with the clinical outcome in post-operative HCC patients with adjuvant IFN-α therapy.
Read the detailed description
- TREATMENT PLAN 1.1 Eligible patients are randomized to receive adjuvant IFN-α for 53 wks or 1.2 Administration of IFN-α 1.21 IFN-α will be started after randomization. 1.22 IFN-α will be administered by subcutaneous injection at the bed time. 1.23 Escalation of IFN-α dosage. 1.231 During the first 2 days, 1 x 106 u/day will be given. 1.232 If tolerable, the dose of IFN-α will be escalated to 3 x 106 u/day in days 3 and 4, and to 5 x 106 u/day at day 5. 1.24 After dose escalation, IFN-α 5 x 106 u/day will be given in the following ways 1.241 induction therapy: 5 times per week for the first 4 weeks, followed by 1.242 maintenance therapy: 3 times per weeks for additional 48 weeks. 1.25 Modification of IFN-α dosage 1.251 In the presence of any moderate adverse events (as listing in Appendix II) it required a dose reduction to 3 x 106 u/day. 1.2511 If any moderate adverse events occur at the 3 x 106 u/day level, the patients will be withdraw from the study; 1.252 In the presence of any severe adverse events (as listing in Appendix II), it requires immediate discontinuation of therapy; 1.2521 IFN-α will be discontinued until a return to baseline or moderate toxicity. Then IFN-α will be reinstituted at the dose level of 3 x 106 u/day; 1.2522 If moderate or severe adverse events occur at the 3 x 106 u/day level, the patients will be withdraw from the study. 1.253 Flare-up of hepatitis activity, as manifested by increment of serum transaminase per se is not an indication for dose modification; 1.254 If symptoms/signs (S/S) of hepatic decompensation occur after the presence of ALT flare-up during IFN-α therapy, the drug will be held. 1.2541 The presence of two of following five criteria is considered as evidence of hepatic decompensation: 1.25411 Presence of ascites; 1.25412 Presence of hepatic encephalopathy; 1.25413 hypoalbuminemia with serum albumin < 3 g/dl; 1.25414 hyperbilirubinemia with serum bilirubin > 3 mg/dl; 1.25415 Prolongation of prothrombin time with PT > 2 sec above base-line. 1.2542 Serial workup have to be taken to rule out the presence of other predisposing factor (such as spontaneous bacterial peritonitis, constipation, electrolyte imbalance,...ect) to cause the S/S of hepatic decompensation. If any, start specific treatment. 1.2543 If S/S of hepatic decompensation recovered with a return of serum ALT to ≦1.5 times upper limit of normal range, IFN-α will be restarted at the level of 3 x 106 u/day and escalated to 5 x 106 u/day within 1 week. 1.2544 If S/S of hepatic decompensation recovered with persistent elevation of serum ALT > 1.5 times upper limit of normal range, IFN-α will be given and maintained at the level 3 x 106 u/day 3 times per week. 1.2545 After excluding other specific etiologies and S/S of hepatic decompensation persist longer than 4 weeks, patients will be withdrawn from the study. 1.2546 Recurrent episodes of hepatic decompensation will be considered as severe adverse events and managed as listing in section 5.252. 1.255 If symptoms/signs (S/S) of hepatic decompensation occur in the absence of ALT flare-up, the patients will be managed as listing in section 5.252. 1.256 In the presence of severe bacterial infection such as: bacterial peritonitis, bacterial pneumonia, and .. etc., IFN-a will be held until resolution of infection after adequate antibiotics therapy. Then the patients will be managed as listing in section 5.252. 1.26 Before IFN-α, if necessary patients will be pretreated with acetaminophen 500 - 1,000 mg, q 6 hours for 4 doses, started 12 hours before IFN-α administration to alleviate the associated flu-like symptoms. 1.3 Adverse Drug Reaction (ADR) Reports 1.31 Any life threatening and/or unexpected and serious (grade 3 or 4) toxicity will be reported within 48 hours to the principal investigator: Li-Tzong Chen M.D. Cancer Clinical Research Center, National Health Research Institutes, A191 Ward Veteran General Hospital Taipei, 201, Shih-Pai Road, Sec 2, Taipei 112, Taiwan Tel:886-2-8712121-2737; Fax: 886-2-8716467; and/or Per-Jei Chen, M.D., Ph.D. Department of Internal Medicine, National Taiwan University Liver Disease Research Center, National Taiwan University Hospital. Tel: 886-2-3970800-7072 Fax: 886-2-3317624. The initial contact should be made by calling the Coordinate Center of TCOG,at 886-2-7852459. A written report will follow within 7 working days. 1.32 A written report will be submitted within 7 working days describing any life-threatening or lethal (grade 4 or 5) known reactions (except for grade 4 myelosuppression), and any grade 2 or 3 unknown reactions. The address for submitting ADR reports is: Coordinate Center of TCOG, National Health Research Institutes in Biomedical Science, Academia Sinica, Taipei, Taiwan. 1.33 Above toxicity grading is according to the ECOG toxicity criteria (Appendix III) 2.0 Evaluation The following tests should be performed within 2 weeks before the initiation of therapy ( as the baseline data) and then repeated as request following the initiation of therapy. 2.1 Physical examination and comprehensive history are recorded bi-weekly during induction period (first month) and monthly during maintenance therapy (for one year). After first year, patients will be followed bi-monthly. After 6 years , patients will be followed 3 monthly. 2.2 Complete blood count and liver functional tests (bilirubin direct/indirect, AST/ALT and alkaline phosphatase/gGT albumin AC sugar) will be checked bi-weekly during induction period (first month) and monthly during maintenance therapy (for one year). After first year, patients will be followed bi-monthly. After 6 years, patients will be followed 3 monthly.. 2.3 Chest PA every 4 months for one year and then every 6 months. 2.4 ECG for those with history of cardiac disease at time of symptom recurrence. 2.5 a-fetoprotein will be checked monthly for one year and then bi-monthly. After 6 years, patients will be followed 3 monthly. 2.6 Abdominal sonography every 2 months. After 6 years, patients will be followed 3 monthly. 2.7 Abdominal computed tomography performed every 12 months or whenever abdominal sonography shows suspicious recurrent lesions. 2.8 Any suspicious lesion found on abdominal sonography and/or computed tomography should undergo angiography and sono-guided biopsy for histological examination. 2.9 UGI endoscopy at the time of UGI bleeding or dyspepsia. [CANCEAL] 2.91 Preoperative endoscopy is acceptable as the base-line data. [CANCEAL] 2.10 Bone scan at the time of symptoms suggest the occurrence of bony metastases. 2.11 Serum for HBV and HCV status study collected bi-monthly. 2.12 HBeAg and anti-HBe will be checked every 4 months in those with HBeAg(+). After 6 years, patients will be followed 6 monthly. 2.13 HBsAg will be checked every 6 months in those with HBsAg(+). 3.0 Off-study Criteria 3.1 Development of a serious medical condition which makes administration of IFN-α life threatening. 3.11 Patients present with S/S of hepatic decompensation should be managed as list in sections 5.2544 and 5.2545. 3.12 as those listed in 5.2511 and 5.2522. 3.2 Occurrence of tumor recurrence. 3.3 Non-compliance by a patient with protocol requirement. 3.4 Patient refusal further therapy. 3.5 Patient death. 3.6 Interruption of IFN-α therapy >4 weeks 4.0 Statistical Consideration 4.1 Sample size Review of literatures showed that the 2-year survival rate of post-operative HCC was 25% to 60% [7-14]. We estimate that adjuvant IFN-α can improve the 2-year survival rate from 50% to 70%. According to the methods of Casagrande et al.[129], to give a 90% power for detecting the increase of 20% for a two-sided statistical significance test, 134 patients for each of the two treatment arms are needed. 4.2 Randomization Patients are stratified into two strata : one with HBsAg(+),another with HBsAg(-) but with anti-HCV(+). Randomization of patients into control or treatment group is taken within each stratum. Balanced block sizes of two strata for randomization are different. 4.3 Analysis 4.31 The primary objectives are as follows: 4.311 To determine if adjuvant IFN-α can reduce or delay the occurrence in curatively resected HCC. 4.312 To determine if adjuvant IFN-α prolong disease-free survival (DFS) and/or overall survival (OS) in curatively resected HCC. 4.313 To determine the safety and tolerance of IFN-αin post-operative H.C.C patients. 4.314 To evaluate the anti-viral activity of IFN-α in post-operative HCC patients. 4.32 DFS and OS are computed from the date of randomization. 4.321 In analysis of DFS, patients died without disease recurrence will be censored for recurrence at the date of death. 4.322 In analysis of OS, an event is defined as death from any cause. 4.323 The survival distributions of DFS and OS will be estimated by the Kaplan and Meier method [130]. 4 4.324 Statistical comparisons of DFS and OS between the two treatment arms will be performed with the log-rank statistic [131]. 4.325 Cox proportional hazards model [132] will be used to assess the importance of potential prognostic factors, as well as to test the significance of treatment when adjusting for factors. 4.33 Tumor size, Liver inflammation, viral status such as HBsAg. anti- HCVand
- Patient's Specific Factor: Performance status Age Sex Family history of HCC and liver diseases. Esophageal varices Prior Hx of esophageal varices bleeding Serum ALT (SGPT) level Serum albumin level Pre-operative serum α-FP level
- Underlying Liver Disease's Specific Factors: HBsAg (by RIA) HBeAg (by RIA) anti-HBc anti-δ antibody anti-HCV antibody Severity of underlying liver disease in nontumor portion Concurrent management of esophageal varices
- Tumor's Specific Factors: Presence of capsule Tumor type Venous invasion Tumor size (the largest in multiple lesions) Histological grading will be treated as potential prognostic factors. 4.4 Interim Analysis The interim analyses will be conducted according to the alpha spending function approach proposed by DeMets and Lan (1994) which provides flexibility about the time for interim analysis. The a1 spending function, which generates the approximate O'Brien-Fleming boundaries (O'Brien and Fleming, 1979), will be used for a conservation termination at the early stage of the study. In addition, the method of B-value developed by Lan and Wittes (1988), Li (1998) will be used to monitor the data and to compute the conditional probability of detecting either a positive or negative treatment effect at the scheduled end of the study given the present status. The primary efficacy endpoint for the interim analyses is the time to occurrence of second primary tumors. The toxicity will be monitored constantly throughout the study. The conduct of interim analyses and dissemination of the results of the interim analysis will follow the TCOG Data and Safety Monitoring guidelines for confidentiality. The TCOG Data and Safety Monitoring Committee will review the results of interim analyses for a possible early termination of the trial.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- IFN-α2b
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IFN-α2bDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
134 patients for each of the two treatment arms are needed.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
Oct 1997Jul 2005
- First posted8 Sep 2005 (estimated)
- Study startOct 1997
- Study completionJul 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 268 participants
Sponsor and investigators
- Lead sponsor
- National Health Research Institutes, Taiwan
- Sponsor type
- University, hospital or other
- Collaborators
- Chang Gung Memorial Hospital, Tri-Service General Hospital (TSGH), National Taiwan University Hospital, Taipei Veterans General Hospital, Taiwan, Mackay Memorial Hospital, China Medical University Hospital
- Investigators
- Li-Tzong Chen, Ph.D., Study chair, Hepatocellular Carcinoma Postoperative Adjuvant Therapy Disease Committee of TCOGPei-Jer Chen, Ph.D., Study chair, Hepatocellular Carcinoma Postoperative Adjuvant Therapy Disease Committee of TCOG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00149565
- Sponsor's protocol ID
- T1297
- Status last verified
- Dec 2004
- First submitted
- 7 Sep 2005
- Last updated
- 16 Dec 2005
- Results posted
- No
Publications
Chen LT, Chen MF, Li LA, Lee PH, Jeng LB, Lin DY, Wu CC, Mok KT, Chen CL, Lee WC, Chau GY, Chen YS, Lui WY, Hsiao CF, Whang-Peng J, Chen PJ; Disease Committee of Adjuvant Therapy for Postoperative Hepatocellular Carcinoma, Taiwan Cooperative Oncology Group, National Health Research Institutes, Zhunan, Taiwan. Long-term results of a randomized, observation-controlled, phase III trial of adjuvant interferon Alfa-2b in hepatocellular carcinoma after curative resection. Ann Surg. 2012 Jan;255(1):8-17. doi: 10.1097/SLA.0b013e3182363ff9.
PubMed 22104564
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepatocellular Carcinoma Postoperative Adjuvant Therapy Disease Committee of Taiwan Cooperative Oncology Group
- ClinicalTrials.gov ID
- NCT00149565
- Acronym / sponsor ID
- T1297
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 268 participants
- Lead sponsor
- National Health Research Institutes, TaiwanUniversity, hospital or other
- Collaborators
- Chang Gung Memorial Hospital, Tri-Service General Hospital (TSGH), National Taiwan University Hospital, Taipei Veterans General Hospital, Taiwan, Mackay Memorial Hospital, China Medical University Hospital
- Study start
- Oct 1997
- Study completion
- Jul 2005
- First posted
- 8 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- OBJECTIVES
- To investigate whether adjuvant IFN-α therapy can delay or reduce the 2-5 years recurrence rate in curatively resected HCC .
- To examine whether adjuvant IFN-α therapy can prolong the disease-free survival in curatively resected HCC.
- To determine the safety and tolerance of adjuvant IFN-α therapy in postoperative HCC with or without cirrhosis.
- To investigate the change of activity of HBV and HCV in postoperative HCC patients with adjuvant IFN-α therapy.
- To correlate the changes of viral status with the clinical outcome in post-operative HCC patients with adjuvant IFN-α therapy.
Detailed description
- TREATMENT PLAN 1.1 Eligible patients are randomized to receive adjuvant IFN-α for 53 wks or 1.2 Administration of IFN-α 1.21 IFN-α will be started after randomization. 1.22 IFN-α will be administered by subcutaneous injection at the bed time. 1.23 Escalation of IFN-α dosage. 1.231 During the first 2 days, 1 x 106 u/day will be given. 1.232 If tolerable, the dose of IFN-α will be escalated to 3 x 106 u/day in days 3 and 4, and to 5 x 106 u/day at day 5. 1.24 After dose escalation, IFN-α 5 x 106 u/day will be given in the following ways 1.241 induction therapy: 5 times per week for the first 4 weeks, followed by 1.242 maintenance therapy: 3 times per weeks for additional 48 weeks. 1.25 Modification of IFN-α dosage 1.251 In the presence of any moderate adverse events (as listing in Appendix II) it required a dose reduction to 3 x 106 u/day. 1.2511 If any moderate adverse events occur at the 3 x 106 u/day level, the patients will be withdraw from the study; 1.252 In the presence of any severe adverse events (as listing in Appendix II), it requires immediate discontinuation of therapy; 1.2521 IFN-α will be discontinued until a return to baseline or moderate toxicity. Then IFN-α will be reinstituted at the dose level of 3 x 106 u/day; 1.2522 If moderate or severe adverse events occur at the 3 x 106 u/day level, the patients will be withdraw from the study. 1.253 Flare-up of hepatitis activity, as manifested by increment of serum transaminase per se is not an indication for dose modification; 1.254 If symptoms/signs (S/S) of hepatic decompensation occur after the presence of ALT flare-up during IFN-α therapy, the drug will be held. 1.2541 The presence of two of following five criteria is considered as evidence of hepatic decompensation: 1.25411 Presence of ascites; 1.25412 Presence of hepatic encephalopathy; 1.25413 hypoalbuminemia with serum albumin < 3 g/dl; 1.25414 hyperbilirubinemia with serum bilirubin > 3 mg/dl; 1.25415 Prolongation of prothrombin time with PT > 2 sec above base-line. 1.2542 Serial workup have to be taken to rule out the presence of other predisposing factor (such as spontaneous bacterial peritonitis, constipation, electrolyte imbalance,...ect) to cause the S/S of hepatic decompensation. If any, start specific treatment. 1.2543 If S/S of hepatic decompensation recovered with a return of serum ALT to ≦1.5 times upper limit of normal range, IFN-α will be restarted at the level of 3 x 106 u/day and escalated to 5 x 106 u/day within 1 week. 1.2544 If S/S of hepatic decompensation recovered with persistent elevation of serum ALT > 1.5 times upper limit of normal range, IFN-α will be given and maintained at the level 3 x 106 u/day 3 times per week. 1.2545 After excluding other specific etiologies and S/S of hepatic decompensation persist longer than 4 weeks, patients will be withdrawn from the study. 1.2546 Recurrent episodes of hepatic decompensation will be considered as severe adverse events and managed as listing in section 5.252. 1.255 If symptoms/signs (S/S) of hepatic decompensation occur in the absence of ALT flare-up, the patients will be managed as listing in section 5.252. 1.256 In the presence of severe bacterial infection such as: bacterial peritonitis, bacterial pneumonia, and .. etc., IFN-a will be held until resolution of infection after adequate antibiotics therapy. Then the patients will be managed as listing in section 5.252. 1.26 Before IFN-α, if necessary patients will be pretreated with acetaminophen 500 - 1,000 mg, q 6 hours for 4 doses, started 12 hours before IFN-α administration to alleviate the associated flu-like symptoms. 1.3 Adverse Drug Reaction (ADR) Reports 1.31 Any life threatening and/or unexpected and serious (grade 3 or 4) toxicity will be reported within 48 hours to the principal investigator: Li-Tzong Chen M.D. Cancer Clinical Research Center, National Health Research Institutes, A191 Ward Veteran General Hospital Taipei, 201, Shih-Pai Road, Sec 2, Taipei 112, Taiwan Tel:886-2-8712121-2737; Fax: 886-2-8716467; and/or Per-Jei Chen, M.D., Ph.D. Department of Internal Medicine, National Taiwan University Liver Disease Research Center, National Taiwan University Hospital. Tel: 886-2-3970800-7072 Fax: 886-2-3317624. The initial contact should be made by calling the Coordinate Center of TCOG,at 886-2-7852459. A written report will follow within 7 working days. 1.32 A written report will be submitted within 7 working days describing any life-threatening or lethal (grade 4 or 5) known reactions (except for grade 4 myelosuppression), and any grade 2 or 3 unknown reactions. The address for submitting ADR reports is: Coordinate Center of TCOG, National Health Research Institutes in Biomedical Science, Academia Sinica, Taipei, Taiwan. 1.33 Above toxicity grading is according to the ECOG toxicity criteria (Appendix III) 2.0 Evaluation The following tests should be performed within 2 weeks before the initiation of therapy ( as the baseline data) and then repeated as request following the initiation of therapy. 2.1 Physical examination and comprehensive history are recorded bi-weekly during induction period (first month) and monthly during maintenance therapy (for one year). After first year, patients will be followed bi-monthly. After 6 years , patients will be followed 3 monthly. 2.2 Complete blood count and liver functional tests (bilirubin direct/indirect, AST/ALT and alkaline phosphatase/gGT albumin AC sugar) will be checked bi-weekly during induction period (first month) and monthly during maintenance therapy (for one year). After first year, patients will be followed bi-monthly. After 6 years, patients will be followed 3 monthly.. 2.3 Chest PA every 4 months for one year and then every 6 months. 2.4 ECG for those with history of cardiac disease at time of symptom recurrence. 2.5 a-fetoprotein will be checked monthly for one year and then bi-monthly. After 6 years, patients will be followed 3 monthly. 2.6 Abdominal sonography every 2 months. After 6 years, patients will be followed 3 monthly. 2.7 Abdominal computed tomography performed every 12 months or whenever abdominal sonography shows suspicious recurrent lesions. 2.8 Any suspicious lesion found on abdominal sonography and/or computed tomography should undergo angiography and sono-guided biopsy for histological examination. 2.9 UGI endoscopy at the time of UGI bleeding or dyspepsia. [CANCEAL] 2.91 Preoperative endoscopy is acceptable as the base-line data. [CANCEAL] 2.10 Bone scan at the time of symptoms suggest the occurrence of bony metastases. 2.11 Serum for HBV and HCV status study collected bi-monthly. 2.12 HBeAg and anti-HBe will be checked every 4 months in those with HBeAg(+). After 6 years, patients will be followed 6 monthly. 2.13 HBsAg will be checked every 6 months in those with HBsAg(+). 3.0 Off-study Criteria 3.1 Development of a serious medical condition which makes administration of IFN-α life threatening. 3.11 Patients present with S/S of hepatic decompensation should be managed as list in sections 5.2544 and 5.2545. 3.12 as those listed in 5.2511 and 5.2522. 3.2 Occurrence of tumor recurrence. 3.3 Non-compliance by a patient with protocol requirement. 3.4 Patient refusal further therapy. 3.5 Patient death. 3.6 Interruption of IFN-α therapy >4 weeks 4.0 Statistical Consideration 4.1 Sample size Review of literatures showed that the 2-year survival rate of post-operative HCC was 25% to 60% [7-14]. We estimate that adjuvant IFN-α can improve the 2-year survival rate from 50% to 70%. According to the methods of Casagrande et al.[129], to give a 90% power for detecting the increase of 20% for a two-sided statistical significance test, 134 patients for each of the two treatment arms are needed. 4.2 Randomization Patients are stratified into two strata : one with HBsAg(+),another with HBsAg(-) but with anti-HCV(+). Randomization of patients into control or treatment group is taken within each stratum. Balanced block sizes of two strata for randomization are different. 4.3 Analysis 4.31 The primary objectives are as follows: 4.311 To determine if adjuvant IFN-α can reduce or delay the occurrence in curatively resected HCC. 4.312 To determine if adjuvant IFN-α prolong disease-free survival (DFS) and/or overall survival (OS) in curatively resected HCC. 4.313 To determine the safety and tolerance of IFN-αin post-operative H.C.C patients. 4.314 To evaluate the anti-viral activity of IFN-α in post-operative HCC patients. 4.32 DFS and OS are computed from the date of randomization. 4.321 In analysis of DFS, patients died without disease recurrence will be censored for recurrence at the date of death. 4.322 In analysis of OS, an event is defined as death from any cause. 4.323 The survival distributions of DFS and OS will be estimated by the Kaplan and Meier method [130]. 4 4.324 Statistical comparisons of DFS and OS between the two treatment arms will be performed with the log-rank statistic [131]. 4.325 Cox proportional hazards model [132] will be used to assess the importance of potential prognostic factors, as well as to test the significance of treatment when adjusting for factors. 4.33 Tumor size, Liver inflammation, viral status such as HBsAg. anti- HCVand
- Patient's Specific Factor: Performance status Age Sex Family history of HCC and liver diseases. Esophageal varices Prior Hx of esophageal varices bleeding Serum ALT (SGPT) level Serum albumin level Pre-operative serum α-FP level
- Underlying Liver Disease's Specific Factors: HBsAg (by RIA) HBeAg (by RIA) anti-HBc anti-δ antibody anti-HCV antibody Severity of underlying liver disease in nontumor portion Concurrent management of esophageal varices
- Tumor's Specific Factors: Presence of capsule Tumor type Venous invasion Tumor size (the largest in multiple lesions) Histological grading will be treated as potential prognostic factors. 4.4 Interim Analysis The interim analyses will be conducted according to the alpha spending function approach proposed by DeMets and Lan (1994) which provides flexibility about the time for interim analysis. The a1 spending function, which generates the approximate O'Brien-Fleming boundaries (O'Brien and Fleming, 1979), will be used for a conservation termination at the early stage of the study. In addition, the method of B-value developed by Lan and Wittes (1988), Li (1998) will be used to monitor the data and to compute the conditional probability of detecting either a positive or negative treatment effect at the scheduled end of the study given the present status. The primary efficacy endpoint for the interim analyses is the time to occurrence of second primary tumors. The toxicity will be monitored constantly throughout the study. The conduct of interim analyses and dissemination of the results of the interim analysis will follow the TCOG Data and Safety Monitoring guidelines for confidentiality. The TCOG Data and Safety Monitoring Committee will review the results of interim analyses for a possible early termination of the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 20 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
Key exclusion criteria (9 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IFN-α2b | Drug | – |
Primary outcome
134 patients for each of the two treatment arms are needed.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2005.
- Derived from this study: PubMed 22104564Chen LT, Chen MF, Li LA, Lee PH, Jeng LB, Lin DY, Wu CC, Mok KT, Chen CL, Lee WC, Chau GY, Chen YS, Lui WY, Hsiao CF, Whang-Peng J, Chen PJ; Disease Committee of Adjuvant Therapy for Postoperative Hepatocellular Carcinoma, Taiwan Cooperative Oncology Group, National Health Research Institutes, Zhunan, Taiwan. Long-term results of a randomized, observation-controlled, phase III trial of adjuvant interferon Alfa-2b in hepatocellular carcinoma after curative resection. Ann Surg. 2012 Jan;255(1):8-17. doi: 10.1097/SLA.0b013e3182363ff9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Li-Tzong Chen, Ph.D. study chair
Hepatocellular Carcinoma Postoperative Adjuvant Therapy Disease Committee of TCOG
Pei-Jer Chen, Ph.D. study chair
Hepatocellular Carcinoma Postoperative Adjuvant Therapy Disease Committee of TCOG
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing IFN-α2b in people with Hepatocellular Carcinoma, run by National Health Research Institutes, Taiwan at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2005. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
134 patients for each of the two treatment arms are needed.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00149565, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2005.