Irradiation Stent Placement Plus TACE for HCC and PVTT

NCT ID: NCT03730675

Last Updated: 2018-12-21

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

NA

Total Enrollment

308 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-10

Study Completion Date

2021-11-10

Brief Summary

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The study is a multicenter, randomized (1:1), open-label, parallel-arm, Phase 3 clinical trial to evaluate the efficacy and safety of portal irradiation stent placement plus TACE compared to sorafenib plus TACE in patients with advanced HCC accompanied by portal vein tumor thrombosis. Patients will be randomized to receive either portal irradiation stent placement plus TACE(Arm A) or Sorafenib plus TACE (Arm B).

Detailed Description

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The prognosis of HCC with portal vein tumor thrombosis (PVTT) is dismal, with a median survival of 2.7-4.0 months compared to that of 10.0-24.0 months without PVTT. Therefore, the presence of PVTT is regarded as a hallmark of advanced HCC and has a high incidence of 39-63%.

PVTT can accompany intrahepatic tumor spread, liver function deterioration, and portal vein hypertension, and can lead to intractable ascites, variceal rupture, hepatic encephalopathy and/or death. As recommended by the Barcelona Clinic Liver Cancer (BCLC) group, the current standard treatment of HCC with PVTT is sorafenib only. However, sorafenib monotherapy does not achieve satisfactory outcomes, yielding a median survival time of 5.6 to 8.1 months. To improve the prognosis, transarterial chemoembolization (TACE), surgical resection, radiotherapy, ablations, and radioembolization have been applied to treat patients with HCC and PVTT, with improved outcomes reported.

Portal vein stent placement is regarded as a safe and effective technique in relieving portal hypertension, extending treatment options, and prolonging survival in patients with HCC and PVTT. However, the reported stent patency period of 3.7 months and survival time of 2.2 to 6.1 months may not be interpreted as satisfactory outcomes, mainly limited by rapid tumor infiltration and/or subsequent thrombosis formation.

An irradiation stent has been developed and confirmed to be safe and effective in treating unresectable esophageal cancer. A modified irradiation stent designed for biliary tract obstruction was subsequently developed and resulted in significantly improved outcomes in a single-institute randomized, controlled study of patients with malignant biliary obstruction. This study aims to demonstrate that overall survival on portal irradiation stent placement plus TACE is superior to overall survival on sorafenib plus TACE in patients with advanced hepatocellular carcinoma accompanied by portal vein tumor thrombosis. Secondary Objectives includes 1. To compare time to progression between both treatment groups; 2. To compare hepatic function between both treatment groups; 3.To compare the disease control rate of the intrahepatic lesions between both treatment groups; 4.To evaluate and compare the safety and tolerability of both treatment groups; 5. To compare portal patency both treatment groups.

Conditions

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Hepatocellular Carcinoma Portal Vein Tumor Thrombosis

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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irradiation stent plus TACE

Portal irradiation stent placement will be performed before TACE procedures.

Group Type EXPERIMENTAL

Portal irradiation stent placement

Intervention Type PROCEDURE

The irradiation portal vein stent was designed as two separate parts that consisted of an outer seeds-loaded-stent and an inner self-expandable metallic stent

TACE

Intervention Type PROCEDURE

TACE is a minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply.

Sorafenib plus TACE

TACE will be performed in patients randomized to Arm B, with sequential sorafenib.

Group Type ACTIVE_COMPARATOR

TACE

Intervention Type PROCEDURE

TACE is a minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply.

Sorafenib

Intervention Type DRUG

Sorafenib is a kinase inhibitor drug approved for the treatment of advanced hepatocellular carcinoma.

Interventions

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Portal irradiation stent placement

The irradiation portal vein stent was designed as two separate parts that consisted of an outer seeds-loaded-stent and an inner self-expandable metallic stent

Intervention Type PROCEDURE

TACE

TACE is a minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply.

Intervention Type PROCEDURE

Sorafenib

Sorafenib is a kinase inhibitor drug approved for the treatment of advanced hepatocellular carcinoma.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* •

1. Histologically-confirmed or clinical diagnosis of hepatocellular carcinoma (HCC)
2. Histologically-confirmed or imaging-based diagnosis malignant portal vein tumor thrombosis(PVTT)
3. Portal trunk invaded tumor thrombosis without the infiltration of superior mesenteric vein or inferior caval vein
4. At least one patent first branch of the portal vein
5. Measurable intrahepatic disease according to mRECIST
6. Child-Pugh class A or B
7. Eighteen years of age or older
8. With an expected lifespan more than 3 months
9. ECOG performance status 0, 1 or 2
10. Required baseline laboratory data within the following parameters:

1\. Neutrophils ≥ 1.0×10⁹/L 2. Platelets ≥ 50×10⁹ /L 3. Hemoglobin ≥ 90 g/L 4. Serum aspartate aminotransferase (AST; ALT≤5 x ULN) 5. Serum creatinine ≤1.5 x ULN 6. INR \<1.7 or prothrombin time (PT) \< 4 seconds above ULN 7. Total bilirubin \< 34.2 umol/L(2 mg/dL) 11. Signed and dated informed consent and willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria

1. Presence of distant metastasis outside liver or diagnosis of any second malignancy beyond HCC
2. Less than 30% volume of uninvolved liver
3. Prior systemic treatment, including prior treatment with sorafenib or any prior local therapy (such as surgery, radiation therapy, hepatic arterial embolization, TACE, hepatic arterial infusion, radiofrequency ablation, percutaneous ethanol injection or cry ablation)
4. Presence of clinically relevant ascites (that can be classified as Child-Pugh score of 3).
5. Documented variceal hemorrhage within 6 months of study entry or presence of esophageal varices at risk of bleeding (as documented by endoscopy/CT/fluoroscopy)
6. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study entry
7. Any of the following within the 3 months prior to study drug administration: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, including transient ischemic attack, or pulmonary embolism.
8. Ongoing cardiac dysrhythmias of NCI CTCAE grade≥2, atrial fibrillation of any grade, or prolongation of the QTc interval to \> 450 msec for males or \> 470 msec for females.
9. Hypertension that cannot be controlled by medications (blood pressure \>150/100 mm Hg despite optimal medical therapy).
10. Concomitant treatment with botanical formulation having an approved indication for cancer treatment, such as "Xiao Chai Hu Tang", "Kanglaite", "Huai Er Ke Li"etc.
11. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
12. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the 7 days prior to study enrollment.
13. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Zhongda Hospital

OTHER

Sponsor Role lead

Responsible Party

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Gao-jun Teng

President

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gao-Jun Teng, M.D.

Role: PRINCIPAL_INVESTIGATOR

Zhongda Hospital

Locations

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Zhong-da Hospital, Southeast University

Nanjing, Jiangsu, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jian Lu, M.D.

Role: CONTACT

Phone: 86+15850654644

Email: [email protected]

Facility Contacts

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Jian Lu, MD

Role: primary

References

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Lu J, Guo JH, Ji JS, Li YL, Lv WF, Zhu HD, Sun JH, Ren WX, Zhang FJ, Wang WD, Shao HB, Cao GS, Li HL, Gao K, Yang P, Yin GW, Zhu GY, Wu FZ, Wang WJ, Lu D, Chen SQ, Min J, Zhao Y, Li R, Lu LG, Lau WY, Teng GJ. Irradiation stent with 125 I plus TACE versus sorafenib plus TACE for hepatocellular carcinoma with major portal vein tumor thrombosis: a multicenter randomized trial. Int J Surg. 2023 May 1;109(5):1188-1198. doi: 10.1097/JS9.0000000000000295.

Reference Type DERIVED
PMID: 37038986 (View on PubMed)

Other Identifiers

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ZhongdaH-PATENCY

Identifier Type: -

Identifier Source: org_study_id