Clinical trial NCT05788835: DEB-TACE Versus DEB-TACE Sequential HAIC for Unresectable BCLC Stage C HCC; A Randomized Controlled Trial
Official title: Drug-eluting Bead Transarterial Chemoembolization and Drug-eluting Bead Transarterial Chemoembolization Sequential Hepatic Artery Chemotherapy Infusion for Unresectable BCLC Stage C HCC: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: HCC
Keywords: DEB-TACE- HAIC
DEB-TACE
Lead sponsor: The First Affiliated Hospital of Zhengzhou University
Sponsor class: OTHER
First posted: 2023-03-29
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized controlled trial to determine the efficacy and safety of DEB-TACE versus DEB-TACE sequential HAIC for unresectable BCLC stage C HCC

Detailed description: Primary liver cancer is one of the most common malignant tumors in the world. According to the survey results of the BRIDGE study, about 64% of Chinese patients with liver cancer had BCLC stage B and stage C at the first diagnosis, and the vast majority of patients in the middle and advanced stages were no longer suitable for the first choice of surgical resection and should receive comprehensive treatment mainly consisting of local treatment and systemic treatment.

TACE is one of the most used treatments for liver cancer. At present, cTACE and DEB-TACE are mainly used. Drug-eluting beads, as new drug-carrying embolisms, have the advantages of loading chemotherapeutic drugs depending on charge and releasing drugs slowly within a certain time to improve local drug concentration. Based on the application of clinical practice, its efficacy has been well confirmed. DEB-TACE results in better tumor response and a similar safety profile than cTACE. However, for HCC at stage C of BCLC, due to the large tumor load and common portal invasion, it is difficult for a single TACE to achieve complete or partial remission, and a complete embolization is likely to increase the risk of serious complications.

Hepatic Arterial Infusion Chemotherapy is used to treat hepatic arterial infusion chemotherapy (HCC). HAIC requires chemotherapy drugs to be injected directly into the liver tumor via a percutaneous arterial cannula. HAIC drugs alone stay in the tumor for a short time, will be washed out quickly, and cannot be completely covered for tumors with external hepatic collateral circulation. However, unlike HAIC, DEB-TACE can embolize tumors to nourish arteries, rapidly lead to massive ischemic necrosis of tumors, and significantly prolong the contact time between cancer cells and chemotherapy drugs. In conclusion, the combination of DEB-TACE and HAIC can make up for the respective deficiencies of DEB-TACE and HAIC. And produce enhanced local anti-tumor effect and less AEs, especially in HCC with high tumor load.

The combination of DEB-TACE and HAIC has been well tolerated in the treatment of large liver cancer. However, most patients with BCLC stage C HCC have vascular invasion or extrahepatic metastasis, which cannot be treated surgically. Moreover, the progressive involvement of vascular invasion will eventually reduce blood flow and further deteriorate liver function, resulting in impaired liver function and poor prognosis. Therefore, we predict that the DEB-TACE sequential HAIC approach will reduce AEs while achieving good efficacy.

Therefore, based on previous studies, this study intended to select patients with unresectable primary liver cancer at stage C of BCLC in a multi-center setting, and prospectively observe the efficacy of DEB-TACE followed by FOLFOX-based HAIC in the treatment of unresectable BCLC stage C patients.

Eligibility criteria: Inclusion Criteria:

1. Patient with unresectable HCC who strictly meet the clinical diagnostic criteria of the Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2022 Edition) or who have been confirmed by histopathology or cytology, There was at least one measurable lesion (according to the requirements of mRECIST 1.1, the spiral CT scan diameter of the measurable lesion was ≥10mm or the short diameter of enlarged lymph node was ≥15mm).
2. The sum of the diameter of single or 2-3 tumors ≥5cm. Tumor stage: Stage C of BCLC.
3. Patient age between 18 and 75，male or female.
4. ECOG 0-1.
5. Expected life span ≥ 3 months.
6. No history of severe comorbidities, such as hypertension, coronary heart disease, and mental illness, and no history of severe allergies.
7. Child-Pugh A-B.
8. HBV DNA\<2000 IU/ml.
9. Women of childbearing age must undergo a pregnancy test within 7 days prior to enrollment.
10. Patients sign informed consent, good compliance, cooperate with treatment.

Exclusion Criteria:

1. Imaging examinations were conducted for HCC patients with large liver tumors (≥60% of liver volume), or carcinoma thrombus in main portal vein (occupying ≥50% of vascular diameter), or carcinoma thrombus invading mesenteric vein or inferior vena cava, or significant arteriovenous/venous fistula.
2. Before participating in this study, she had received local treatment such as TACE, external radiotherapy and radioactive particle implantation, and had undergone systemic chemotherapy, oral liver cancer targeting drugs (Sorafenib, Lenfacitinib, Apatinib) and immunotherapy such as PD-1/PD-L1/CDLA-4.
3. Diffuse liver cancer patients.
4. Patients with grade Ⅱ or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥450ms for men and 470ms for women.
5. A history of gastrointestinal bleeding within the past 6 months or a definite tendency to gastrointestinal bleeding.
6. Abnormal clotting function, bleeding tendency or receiving thrombolytic or anticoagulant therapy.
7. Patients with central nervous system metastases or known brain metastases. Co-infected patients with HIV; Pregnant or lactating patients. Patients preparing for liver transplantation (other than those with previous liver transplantation.
8. Systemic failure, estimated survival time \<3 months.
9. Severe renal dysfunction.
10. The patients could not complete the treatment plan due to various reasons, and lost control within three months after enrollment.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Time from the first DEB-TACE treatment to either radiological progression or death or up to 36 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Time from the first DEB-TACE treatment to death or up to 36 months
measure: Objective response rate (ORR)
timeFrame: 1, 3, 6,12 months after the first DEB-TACE treatment, up to death or 36 months, whichever came first
measure: Disease control rate (DCR)
timeFrame: 1, 3, 6,12 months after the first DEB-TACE treatment, up to death or 36 months, whichever came first
measure: Time to Progression (TTP)
timeFrame: Time from the first DEB-BACE treatment to either radiological progression up to 36 months
Other outcomes:
Locations:
city: Luohe
country: China
facility: Luo He Central Hospital
state: Henan
city: Luoyang
country: China
facility: Luo Yang Central Hospital
state: Henan
city: Nanyang
country: China
facility: Deng zhou People's Hospital
state: Henan
city: Nanyang
country: China
facility: Nan Yang Central Hospital
state: Henan
city: Pingdingshan
country: China
facility: General Hospital of Pingmei Shenma Group
state: Henan
city: Shangqiu
country: China
facility: First People's Hospital of Shangqiu
state: Henan
city: Shangqiu
country: China
facility: Shangqiu Municipal Hospital
state: Henan
city: Xinyang
country: China
facility: Xin Yang Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: The Fifth Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: Zhengzhou Central Hospital
state: Henan
city: Zhoukou
country: China
facility: Zhou Kou Central Hospital
state: Henan
city: Zhumadian
country: China
facility: First People's Hospital of Zhu Madian
state: Henan
city: Zhumadian
country: China
facility: Zhu Ma Dian Central Hospital
state: Henan
city: Zhumadian
country: China
facility: Zhu Madian Traditional Chinese Medicine Hospital
state: Henan
city: Jiaozuo
country: China
facility: Second People's Hospital of Jiaozuo
Study officials:
affiliation: The First Affiliated Hospital of Zhengzhou University
name: Xuhua Xuhua, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: