Conversion Therapy Using TACE/HAIC With Anti-Angiogenic and Immunotherapy for Initially Unresectable Hepatocellular Carcinoma Achieving Complete Response or Resectability, Followed by Surgery or Continued Systemic Treatment: A Prospective Cohort Study

NCT ID: NCT07206511

Last Updated: 2025-10-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 278 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-10-09
• Study Completion Date: 2028-12-31

Brief Summary

This is a prospective cohort study designed to evaluate the effectiveness and safety of two post-conversion treatment strategies for patients with initially unresectable hepatocellular carcinoma (uHCC). Participants first receive conversion therapy with transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with anti-angiogenic agents and immune checkpoint inhibitors (ICIs). After this therapy, patients who achieve complete radiological response (rCR) or meet resectability criteria will either undergo surgical resection or continue systemic therapy. The study aims to compare outcomes between these two strategies to help guide treatment decisions for advanced liver cancer.

Conditions

Unresectable Hepatocellular Carcinom

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Systemic Therapy Group

Patients with initially unresectable hepatocellular carcinoma who achieved complete radiological response or resectability after TACE/HAIC + anti-angiogenic agents + immune checkpoint inhibitors and then continued systemic therapy.

No interventions assigned to this group

Surgical Resection Group

Patients with initially unresectable hepatocellular carcinoma who achieved complete radiological response or resectability after TACE/HAIC + anti-angiogenic agents + immune checkpoint inhibitors and then underwent surgical resection.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. Signed written informed consent.

2. Age 18-75 years.

3. Hepatocellular carcinoma (HCC) confirmed by histology/cytology or diagnosed according to the AASLD criteria.

4. Initially unresectable HCC (uHCC), defined according to the Chinese Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2024 edition) and the Chinese Expert Consensus on Conversion and Perioperative Therapy for Primary Liver Cancer (2024 edition): HCC considered unsafe for curative resection due to inability to ensure both oncological completeness (R0 resection) and functional hepatic reserve (adequate future liver remnant with good vascular supply and biliary drainage to maintain postoperative liver function and minimize morbidity and mortality). Mainly includes CNLC stage Ib-IIIa or potentially resectable cases. Some stage Ia patients may also be considered uHCC if the tumor is adjacent to major intrahepatic vessels or involves the first/second hepatic hilum making R0 resection infeasible, or if severe cirrhosis increases risk of postoperative liver failure and complications; these can be considered after successful conversion and supportive treatment.

5. No prior systemic therapy before conversion treatment.

6. Conversion therapy regimen must include TACE or HAIC plus anti-angiogenic agents and immune checkpoint inhibitors (ICIs).

7. Anti-angiogenic agents may include lenvatinib, sorafenib, apatinib, donafenib, anlotinib, bevacizumab.

8. ICIs may include pembrolizumab, atezolizumab, nivolumab, sintilimab, tislelizumab, toripalimab, penpulimab, cadonilimab, KN-046.

9. After conversion therapy, hepatic lesions achieve radiological complete response (rCR) by mRECIST criteria on contrast-enhanced CT or MRI, or are assessed to have reached resectability criteria (eligible for curative hepatectomy or downstaging enabling safe surgery).

10. After achieving rCR or resectability, patients must have received either liver resection or continued systemic therapy with scheduled follow-up.

11. Child-Pugh class A or B liver function.

12. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.

Exclusion Criteria

1. Presence of another primary malignancy in other organs.

2. History of other malignancies.

3. Recurrent HCC occurring <2 years after previous curative surgery or adjuvant therapy.

4. Received treatments other than TACE or HAIC plus anti-angiogenic agents and ICIs during the conversion phase.

5. Received treatments during postoperative or maintenance systemic therapy that differ from the initial conversion regimen.

6. Severe organ dysfunction.

7. Incomplete radiological assessment data after treatment.

8. Child-Pugh class C liver function.

9. Pregnant or breastfeeding women.

10. Patients undergoing only functional future liver remnant (FLR) hypertrophy procedures (e.g., ALPPS or PVE) for insufficient FLR without other criteria for uHCC conversion.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jian Zhou

Hospital President

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Ao Huang, PhD

Role: CONTACT

huang.ao@zs-hospital.sh.cn

+86-21-64041990

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

B2025-437R

Identifier Type: -

Identifier Source: org_study_id