Transcatheter Arterial Chemoembolization Therapy In Combination With Sorafenib (TACTICS)
Primary Purpose
Hepatocellular Carcinoma, Unresectable Hepatocellular Carcinoma, Carcinoma, Hepatocellular
Status
Unknown status
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
TACE with sorafenib
TACE alone
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Transcatheter arterial chemoembolization, TACE, sorafenib, Time to untreatable progression, TTUP
Eligibility Criteria
Inclusion Criteria:
- Patients aged 20 Years or over
- Patients who were fully informed of the study beforehand and signed the informed consent to participate in the study.
- Patients who are expected to live more than 12 weeks.
- Patients diagnosed with typical HCC by biopsy,cytology, or diagnostic imaging such as dynamic CT(MRI).Typical HCC is defined by AASLD criteria.
- Patients in whom complete resection of the tumor by hepatectomy or complete tumor necrosis by local tumor necrosis therapy(RFA) cannot be expected to succeed.
- Patients with tumors which are confirmed to the liver and can be treated by TACE(the maximum diameter equal to or less than 10cm,and the maximum number of nodule equal to or less than 10).
- Patients with viable and measurable target lesion.
- patients with no or one history of TACE therapy.
- patients with an ECOG PS(Performance Status) Score of 0 or 1.
- patients with Child-Pugh class A.
Patients with laboratory values that meet the following criteria:
- Hemoglobin ≥ 8.5 g/dl
- Granulocytes ≥ 1500/mm3
- Platelet count ≥ 50,000 /mm3
- Total serum bilirubin ≤ 3 mg/dl
- AST and ALT ≤ 6 times upper limits of normal
- Serum creatinine ≤ 1.5 times upper limits of normal
Exclusion Criteria:
History of malignant tumor, excluding the following cases:
- Curatively treated early stage cancer with a low risk of recurrence ,such as carcinoma in situ of the cervix, basal cell carcinoma, superficial bladder tumor, and early gastric cancer.
- Malignant tumor that was curatively treated more than 3 years prior to study entry and has not recurred since then
Cardiac disease that meet any of the following criteria:
- NYHA Class III or higher congestive heart failure
- History of symptomatic coronary artery disease or myocardial infarction within 6 months before enrollment
- Arrhythmia requiring control by antiarrhythmic drugs such as beta-blockers or digoxin
- Serious and active infection, except for HBV and HCV
- History of HIV infection
- Renal dialysis
- Diffuse tumor lesion
- Extrahepatic metastasis
- Vascular invasion
- Intracranial tumor
- Preexisting or history of hepatic encephalopathy
- Clinically uncontrolled ascites or pleural effusion
- Clinically severe gastrointestinal bleeding within 4 weeks of the start of treatment
- Esophageal and/or gastric varices which has high risk of bleeding
- History of thrombosis and/or embolism within 6 months of the start of treatment
History of receiving any of the following therapies:
- Systemic chemotherapy for advanced HCC(including sorafenib therapy)
- Local therapy, such as radiofrequency ablation, TACE, or hepatic arterial infusion within 3 months of the start of treatment
- Current treatment with CYP3A4 inducing agents
- Invasive surgery within 4 weeks of the start of treatment
- History of allogenic transplantation
- History of bone marrow transplant or haemopoietic stem cell transplant within 4 weeks of the start of this study
- Unable to take oral medications
- Gastrointestinal problems that may affect absorption or pharmacokinetics of the study drugs
- Use of drugs that may affect absorption or pharmacokinetics of the study drugs
- Concurrent disease or disability that may affect evaluation of the effects of the study drugs
- Enrollment in another study within 4 weeks of study entry
- Female patients who are pregnant, lactating, possibly pregnant, or planning to become pregnant
- Risk of allergic reactions to the study drugs
- Drug abuse or other physical, psychological , or social problems that may interfere with the participation in the study or evaluation of study results
- Any condition that could jeopardize the safety of the patient or their compliance in the study
Sites / Locations
- Kinki University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
TACE with sorafenib
TACE alone
Arm Description
TACE(on demand) with sorafenib till untreatable progression
TACE(on demand) till unreatable progression
Outcomes
Primary Outcome Measures
Progression Free Survival
Patients will be evaluated for these endpoints every 8 weeks
Overall Survival
The overall survival is defined as time from randomization to death due to any cause, and will be evaluated every 8 weeks in the protocol treatment, and every one year in the follow-up period,respectively.
Secondary Outcome Measures
Time To Progression
Time to progression is defined as time from randomization to radiological progression and will be evaluated every 8 week.
Objective Response Rate
Objective Response Rate is defined as best response
Tumor markers
Change of tumor markers
Safety
Number of participants with adverse events as a measure of safety and tolerability(According to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0)
Time To Untreatable Progression(TTUP)
Time to untreatable progression is defined as time from randomization to untreatable progression and will be evaluated every 8 week.
Time to Child-Pugh C
Time to Child-Pugh C is defined as time from randomization to Child-Pugh C and will be evaluated every 8 week.
Time to intrahepatic tumor progression
Time to intrahepatic tumor progression is defined as time from randomization to intrahepatic tumor progression and will be evaluated every 8 week.
Time to vascular invasion
Time to vascular invasion is defined as time from randomization to vascular invasion and will be evaluated every 8 week.
Time to Extrahepatic spread
Time to extrahepatic spread is defined as time from randomization to extrahepatic spread and will be evaluated every 8 week.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01217034
Brief Title
Transcatheter Arterial Chemoembolization Therapy In Combination With Sorafenib
Acronym
TACTICS
Official Title
Phase II Study: Transcatheter Arterial Chemoembolization Therapy In Combination With Sorafenib (TACTICS)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Unknown status
Study Start Date
October 2010 (undefined)
Primary Completion Date
March 2018 (Anticipated)
Study Completion Date
March 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Kindai University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of the combination therapy with Transcatheter Arterial Chemoembolization (TACE) and sorafenib compared to TACE alone in patients with unresectable hepatocellular carcinoma (HCC) who are not candidates for surgical resection or percutaneous ablation therapy.
Detailed Description
TACE with sorafenib Group
Sorafenib will be administrated at a dose of 400mg o.d. before the first TACE. After 2days drug rest, TACE will be conducted. Sorafenib will be resumed at a dose of 400mg o.d. from 3 days after TACE(the resumption day can be postponed until 21 days after TACE). When tolerability is confirmed at 1 week after resumption, the dose of sorafenib will be increased to 400mg b.i.d. When tumor increases, TACE will be repeated.
Control group
TACE will be conducted at scheduled day. When tumor increases, TACE will be repeated.
The treatment regimen will be continued until untreatable progression which is defined as follows:
Child-Pugh grade C
Tumor growth (125 percent from baseline status)
Vascular invasion(Vp3,Vp4)
Extra hepatic spread which size is more than 10mm
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Unresectable Hepatocellular Carcinoma, Carcinoma, Hepatocellular, Liver Neoplasm
Keywords
Transcatheter arterial chemoembolization, TACE, sorafenib, Time to untreatable progression, TTUP
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
228 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
TACE with sorafenib
Arm Type
Experimental
Arm Description
TACE(on demand) with sorafenib till untreatable progression
Arm Title
TACE alone
Arm Type
Active Comparator
Arm Description
TACE(on demand) till unreatable progression
Intervention Type
Drug
Intervention Name(s)
TACE with sorafenib
Other Intervention Name(s)
TACE with Nexavar
Intervention Description
Sorafenib will be administrated at a dose of 400mg o.d. before the first TACE. After 2days drug rest, TACE will be conducted. Sorafenib will be resumed at a dose of 400mg o.d. from 3 days after TACE(the resumption day can be postponed until 21 days after TACE). When tolerability is confirmed at 1 week after resumption, the dose of sorafenib will be increased to 400mg b.i.d. When tumor increases, TACE will be repeated.
Intervention Type
Procedure
Intervention Name(s)
TACE alone
Other Intervention Name(s)
TACE
Intervention Description
TACE will be conducted at scheduled day. When tumor increases, TACE will be repeated.
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
Patients will be evaluated for these endpoints every 8 weeks
Time Frame
every 8 week
Title
Overall Survival
Description
The overall survival is defined as time from randomization to death due to any cause, and will be evaluated every 8 weeks in the protocol treatment, and every one year in the follow-up period,respectively.
Time Frame
every 8 week
Secondary Outcome Measure Information:
Title
Time To Progression
Description
Time to progression is defined as time from randomization to radiological progression and will be evaluated every 8 week.
Time Frame
every 8 weeks
Title
Objective Response Rate
Description
Objective Response Rate is defined as best response
Time Frame
4week after TACE
Title
Tumor markers
Description
Change of tumor markers
Time Frame
every 4 weeks
Title
Safety
Description
Number of participants with adverse events as a measure of safety and tolerability(According to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0)
Time Frame
every 4 weeks
Title
Time To Untreatable Progression(TTUP)
Description
Time to untreatable progression is defined as time from randomization to untreatable progression and will be evaluated every 8 week.
Time Frame
every 8 week till untreatable progression, assessed up to 100 months
Title
Time to Child-Pugh C
Description
Time to Child-Pugh C is defined as time from randomization to Child-Pugh C and will be evaluated every 8 week.
Time Frame
every 8 week till liver deterioration to Child-Pugh C, assessed up to 100 months
Title
Time to intrahepatic tumor progression
Description
Time to intrahepatic tumor progression is defined as time from randomization to intrahepatic tumor progression and will be evaluated every 8 week.
Time Frame
every 8 week till intrahepatic tumor progression, assessed up to 100 months
Title
Time to vascular invasion
Description
Time to vascular invasion is defined as time from randomization to vascular invasion and will be evaluated every 8 week.
Time Frame
every 8 week till vascular invasion, assessed up to 100 months
Title
Time to Extrahepatic spread
Description
Time to extrahepatic spread is defined as time from randomization to extrahepatic spread and will be evaluated every 8 week.
Time Frame
every 8 week till extrahepatic spread, assessed up to 100 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients aged 20 Years or over
Patients who were fully informed of the study beforehand and signed the informed consent to participate in the study.
Patients who are expected to live more than 12 weeks.
Patients diagnosed with typical HCC by biopsy,cytology, or diagnostic imaging such as dynamic CT(MRI).Typical HCC is defined by AASLD criteria.
Patients in whom complete resection of the tumor by hepatectomy or complete tumor necrosis by local tumor necrosis therapy(RFA) cannot be expected to succeed.
Patients with tumors which are confirmed to the liver and can be treated by TACE(the maximum diameter equal to or less than 10cm,and the maximum number of nodule equal to or less than 10).
Patients with viable and measurable target lesion.
patients with no or one history of TACE therapy.
patients with an ECOG PS(Performance Status) Score of 0 or 1.
patients with Child-Pugh class A.
Patients with laboratory values that meet the following criteria:
Hemoglobin ≥ 8.5 g/dl
Granulocytes ≥ 1500/mm3
Platelet count ≥ 50,000 /mm3
Total serum bilirubin ≤ 3 mg/dl
AST and ALT ≤ 6 times upper limits of normal
Serum creatinine ≤ 1.5 times upper limits of normal
Exclusion Criteria:
History of malignant tumor, excluding the following cases:
Curatively treated early stage cancer with a low risk of recurrence ,such as carcinoma in situ of the cervix, basal cell carcinoma, superficial bladder tumor, and early gastric cancer.
Malignant tumor that was curatively treated more than 3 years prior to study entry and has not recurred since then
Cardiac disease that meet any of the following criteria:
NYHA Class III or higher congestive heart failure
History of symptomatic coronary artery disease or myocardial infarction within 6 months before enrollment
Arrhythmia requiring control by antiarrhythmic drugs such as beta-blockers or digoxin
Serious and active infection, except for HBV and HCV
History of HIV infection
Renal dialysis
Diffuse tumor lesion
Extrahepatic metastasis
Vascular invasion
Intracranial tumor
Preexisting or history of hepatic encephalopathy
Clinically uncontrolled ascites or pleural effusion
Clinically severe gastrointestinal bleeding within 4 weeks of the start of treatment
Esophageal and/or gastric varices which has high risk of bleeding
History of thrombosis and/or embolism within 6 months of the start of treatment
History of receiving any of the following therapies:
Systemic chemotherapy for advanced HCC(including sorafenib therapy)
Local therapy, such as radiofrequency ablation, TACE, or hepatic arterial infusion within 3 months of the start of treatment
Current treatment with CYP3A4 inducing agents
Invasive surgery within 4 weeks of the start of treatment
History of allogenic transplantation
History of bone marrow transplant or haemopoietic stem cell transplant within 4 weeks of the start of this study
Unable to take oral medications
Gastrointestinal problems that may affect absorption or pharmacokinetics of the study drugs
Use of drugs that may affect absorption or pharmacokinetics of the study drugs
Concurrent disease or disability that may affect evaluation of the effects of the study drugs
Enrollment in another study within 4 weeks of study entry
Female patients who are pregnant, lactating, possibly pregnant, or planning to become pregnant
Risk of allergic reactions to the study drugs
Drug abuse or other physical, psychological , or social problems that may interfere with the participation in the study or evaluation of study results
Any condition that could jeopardize the safety of the patient or their compliance in the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Masatoshi Kudo, Professor
Organizational Affiliation
Kindai University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kinki University Hospital
City
Osaka-Sayama
State/Province
Osaka
ZIP/Postal Code
589-8511
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
35978604
Citation
Kudo M, Ueshima K, Ikeda M, Torimura T, Tanabe N, Aikata H, Izumi N, Yamasaki T, Nojiri S, Hino K, Tsumura H, Kuzuya T, Isoda N, Moriguchi M, Aino H, Ido A, Kawabe N, Nakao K, Wada Y, Ogasawara S, Yoshimura K, Okusaka T, Furuse J, Kokudo N, Okita K, Johnson PJ, Arai Y. Final Results of TACTICS: A Randomized, Prospective Trial Comparing Transarterial Chemoembolization Plus Sorafenib to Transarterial Chemoembolization Alone in Patients with Unresectable Hepatocellular Carcinoma. Liver Cancer. 2022 Feb 10;11(4):354-367. doi: 10.1159/000522547. eCollection 2022 Jul.
Results Reference
derived
PubMed Identifier
31801872
Citation
Kudo M, Ueshima K, Ikeda M, Torimura T, Tanabe N, Aikata H, Izumi N, Yamasaki T, Nojiri S, Hino K, Tsumura H, Kuzuya T, Isoda N, Yasui K, Aino H, Ido A, Kawabe N, Nakao K, Wada Y, Yokosuka O, Yoshimura K, Okusaka T, Furuse J, Kokudo N, Okita K, Johnson PJ, Arai Y; TACTICS study group. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial. Gut. 2020 Aug;69(8):1492-1501. doi: 10.1136/gutjnl-2019-318934. Epub 2019 Dec 4.
Results Reference
derived
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Transcatheter Arterial Chemoembolization Therapy In Combination With Sorafenib
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