Transcatheter Arterial Chemoembolization Therapy In Combination With Sorafenib

NCT ID: NCT01217034

Last Updated: 2017-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

228 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2018-03-31

Brief Summary

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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

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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

Conditions

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Hepatocellular Carcinoma Unresectable Hepatocellular Carcinoma Carcinoma, Hepatocellular Liver Neoplasm

Keywords

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Transcatheter arterial chemoembolization TACE sorafenib Time to untreatable progression TTUP

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TACE with sorafenib

TACE(on demand) with sorafenib till untreatable progression

Group Type EXPERIMENTAL

TACE with sorafenib

Intervention Type DRUG

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.

TACE alone

TACE(on demand) till unreatable progression

Group Type ACTIVE_COMPARATOR

TACE alone

Intervention Type PROCEDURE

TACE will be conducted at scheduled day. When tumor increases, TACE will be repeated.

Interventions

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TACE with sorafenib

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 DRUG

TACE alone

TACE will be conducted at scheduled day. When tumor increases, TACE will be repeated.

Intervention Type PROCEDURE

Other Intervention Names

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TACE with Nexavar TACE

Eligibility Criteria

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Inclusion Criteria

1. Patients aged 20 Years or over
2. Patients who were fully informed of the study beforehand and signed the informed consent to participate in the study.
3. Patients who are expected to live more than 12 weeks.
4. Patients diagnosed with typical HCC by biopsy,cytology, or diagnostic imaging such as dynamic CT(MRI).Typical HCC is defined by AASLD criteria.
5. 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.
6. 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).
7. Patients with viable and measurable target lesion.
8. patients with no or one history of TACE therapy.
9. patients with an ECOG PS(Performance Status) Score of 0 or 1.
10. patients with Child-Pugh class A.
11. Patients with laboratory values that meet the following criteria:

1. Hemoglobin ≥ 8.5 g/dl
2. Granulocytes ≥ 1500/mm3
3. Platelet count ≥ 50,000 /mm3
4. Total serum bilirubin ≤ 3 mg/dl
5. AST and ALT ≤ 6 times upper limits of normal
6. Serum creatinine ≤ 1.5 times upper limits of normal

Exclusion Criteria

1. History of malignant tumor, excluding the following cases:

1. 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.
2. Malignant tumor that was curatively treated more than 3 years prior to study entry and has not recurred since then
2. Cardiac disease that meet any of the following criteria:

1. NYHA Class III or higher congestive heart failure
2. History of symptomatic coronary artery disease or myocardial infarction within 6 months before enrollment
3. Arrhythmia requiring control by antiarrhythmic drugs such as beta-blockers or digoxin
3. Serious and active infection, except for HBV and HCV
4. History of HIV infection
5. Renal dialysis
6. Diffuse tumor lesion
7. Extrahepatic metastasis
8. Vascular invasion
9. Intracranial tumor
10. Preexisting or history of hepatic encephalopathy
11. Clinically uncontrolled ascites or pleural effusion
12. Clinically severe gastrointestinal bleeding within 4 weeks of the start of treatment
13. Esophageal and/or gastric varices which has high risk of bleeding
14. History of thrombosis and/or embolism within 6 months of the start of treatment
15. History of receiving any of the following therapies:

1. Systemic chemotherapy for advanced HCC(including sorafenib therapy)
2. Local therapy, such as radiofrequency ablation, TACE, or hepatic arterial infusion within 3 months of the start of treatment
3. Current treatment with CYP3A4 inducing agents
4. Invasive surgery within 4 weeks of the start of treatment
5. History of allogenic transplantation
6. History of bone marrow transplant or haemopoietic stem cell transplant within 4 weeks of the start of this study
16. Unable to take oral medications
17. Gastrointestinal problems that may affect absorption or pharmacokinetics of the study drugs
18. Use of drugs that may affect absorption or pharmacokinetics of the study drugs
19. Concurrent disease or disability that may affect evaluation of the effects of the study drugs
20. Enrollment in another study within 4 weeks of study entry
21. Female patients who are pregnant, lactating, possibly pregnant, or planning to become pregnant
22. Risk of allergic reactions to the study drugs
23. Drug abuse or other physical, psychological , or social problems that may interfere with the participation in the study or evaluation of study results
24. Any condition that could jeopardize the safety of the patient or their compliance in the study
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kindai University

OTHER

Sponsor Role lead

Responsible Party

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Masatoshi Kudo

Professor, Kindai University Faculty of Medicine, Department of Gastroenterology and Hepatology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Masatoshi Kudo, Professor

Role: PRINCIPAL_INVESTIGATOR

Kindai University

Locations

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Kinki University Hospital

Ōsaka-sayama, Osaka, Japan

Site Status

Countries

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Japan

References

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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.

Reference Type DERIVED
PMID: 35978604 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31801872 (View on PubMed)

Other Identifiers

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JLOG 1001 trial

Identifier Type: -

Identifier Source: org_study_id