Neoadjuvant Therapy in Patients With Resectable HCC Screened by a Multimodal Deep Learning Model

NCT ID: NCT06420440

Last Updated: 2025-05-01

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

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-01

Study Completion Date

2027-05-31

Brief Summary

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Primary liver cancer is one of the most common malignant tumors in the world, and about 80%\~90% of primary liver cancers are pathologically characterized as hepatocellular carcinoma (HCC). Radical surgery is the main method for patients with HCC to obtain long-term survival. However, the early recurrence rate of high-risk HCC is very high, which seriously affects the overall therapeutic effect.

Detailed Description

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The protocol was revised in April 2025 (V1.1). Primary liver cancer is one of the most common malignant tumors in the world, and about 80%\~90% of primary liver cancers are pathologically characterized as hepatocellular carcinoma (HCC). Radical surgery is the main method for patients with HCC to obtain long-term survival. However, the early recurrence rate of high-risk HCC is very high, which seriously affects the overall therapeutic effect. Although the tumor is in BCLC-A stage, when the tumor diameter is more than 5cm, the effect of surgery is worse than that of single small HCC due to the large resection range, the high risk of surgery and residual disease. In addition, BCLC-stage B and C tumors have a high recurrence rate due to multiple lesions or macrovascular invasion. To address this issue, new tools are urgently needed to guide the selection of appropriate treatment regimens to reduce the risk of postoperative recurrence and improve overall survival.

The investigators multidisciplinary team used deep learning technology to construct an artificial intelligence prediction model of neoadjuvant therapy (Neoadj-Net) benefit based on pre-treatment genetic testing data, digital pathology slides and imaging data (enhanced MRI) of 536 intermediate-stage HCC patients treated with HAIC in combination with lenvatinib and PD-1 monoclonal antibody in six centers, and external center data validated the model's good ability to identify the beneficiary population of the combination regimen ( AUC 0.89, Accuracy 0.86). This study is to explore the effectiveness and safety of Neoadj-Net in reducing postoperative recurrence by observing the benefit of the combined neoadjuvant regimen in patients who are potentially benefited from neoadjuvant therapy and direct surgery from the perspective of precision therapy.

Conditions

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HCC

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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Neoadjuvant therapy group

Patients in the neoadjuvant group received neoadjuvant therapy prior to surgery (two cycles of HAIC combined with Tislelizumab and Lenvatinib), and adjuvant therapy (Tislelizumab for 8 cycles) after surgery.

Group Type EXPERIMENTAL

Hepatic arterial infusion chemotherapy

Intervention Type PROCEDURE

Patients in the neoadjuvant group received two cycles of neoadjuvant hepatic arterial infusion chemotherapy (HAIC, adoption of the FOFOLX6 program, Folinic acid+5-fluorouracil+Oxaliplatin, 21 days between second HAIC treatments with a window of ±3 days)

Lenvatinib

Intervention Type DRUG

Patients in the neoadjuvant therapy group received Lenvatinib before surgery(Len was started before HAIC treatment, discontinued during HAIC treatment, and discontinued approximately two weeks before surgery, Oral 8 mg or 12mg once a day depending body weight).

Tislelizumab

Intervention Type DRUG

Patients in the neoadjuvant therapy group received two cycles of Tislelizumab therapy before surgery (First treatment with Tislelizumab was started 0-1 days after HAIC, 200 mg IV, followed by a second treatment 21 days later)

Liver resection

Intervention Type PROCEDURE

Patients in the neoadjuvant therapy group were evaluated for tumor status and surgical safety after neoadjuvant therapy, and eligible patients subsequently underwent surgical resection. Patients in the direct surgery group underwent liver resection.

Tislelizumab

Intervention Type DRUG

Given the high risk of postoperative recurrence, patients in both groups received adjuvant Tis therapy (every 21 days for 8 cycles) starting about one month after surgery.

Direct liver resection group

Patients in the control group underwent liver resection directly and received adjuvant therapy (Tislelizumab for 8 cycles) after surgery.

Group Type ACTIVE_COMPARATOR

Liver resection

Intervention Type PROCEDURE

Patients in the neoadjuvant therapy group were evaluated for tumor status and surgical safety after neoadjuvant therapy, and eligible patients subsequently underwent surgical resection. Patients in the direct surgery group underwent liver resection.

Tislelizumab

Intervention Type DRUG

Given the high risk of postoperative recurrence, patients in both groups received adjuvant Tis therapy (every 21 days for 8 cycles) starting about one month after surgery.

Interventions

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Hepatic arterial infusion chemotherapy

Patients in the neoadjuvant group received two cycles of neoadjuvant hepatic arterial infusion chemotherapy (HAIC, adoption of the FOFOLX6 program, Folinic acid+5-fluorouracil+Oxaliplatin, 21 days between second HAIC treatments with a window of ±3 days)

Intervention Type PROCEDURE

Lenvatinib

Patients in the neoadjuvant therapy group received Lenvatinib before surgery(Len was started before HAIC treatment, discontinued during HAIC treatment, and discontinued approximately two weeks before surgery, Oral 8 mg or 12mg once a day depending body weight).

Intervention Type DRUG

Tislelizumab

Patients in the neoadjuvant therapy group received two cycles of Tislelizumab therapy before surgery (First treatment with Tislelizumab was started 0-1 days after HAIC, 200 mg IV, followed by a second treatment 21 days later)

Intervention Type DRUG

Liver resection

Patients in the neoadjuvant therapy group were evaluated for tumor status and surgical safety after neoadjuvant therapy, and eligible patients subsequently underwent surgical resection. Patients in the direct surgery group underwent liver resection.

Intervention Type PROCEDURE

Tislelizumab

Given the high risk of postoperative recurrence, patients in both groups received adjuvant Tis therapy (every 21 days for 8 cycles) starting about one month after surgery.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Aged 18-75.
2. No previous local or systemic treatment for hepatocellular carcinoma.
3. Child-Pugh liver function score ≤ 7.
4. ECOG PS 0-1.
5. No serious organic diseases of the heart, lungs, brain, kidneys, etc.
6. Enhanced MRI determines that the tumor is technically resectable but at high risk for recurrence(BCLC-A tumor diameter more than or equal to 5cm; BCLC-B; BCLC-C) ; without distant metastasis.
7. Pathologic type of hepatocellular carcinoma confirmed by puncture biopsy.
8. Multimodal Deep Learning Model Screening Based on Pathology, Imaging, and Genetic Data Suggests Benefit from HAIC in Combination with Lenvatinib and PD-1 inhibitors.

Exclusion Criteria

1. Pregnant and lactating women.
2. Suffering from a condition that interferes with the absorption, distribution, metabolism, or clearance of the study drug (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, impaired absorption, etc.).
3. A history of gastrointestinal bleeding within the previous 4 weeks or a definite predisposition to gastrointestinal bleeding (e.g., known locally active ulcer lesions, fecal occult blood ++ or more, or gastroscopy if persistent fecal occult blood +) that has not been targeted, or other conditions that may have caused gastrointestinal bleeding (e.g., severe fundoplication/esophageal varices), as determined by the investigator.
4. Active infection.
5. Other significant clinical and laboratory abnormalities that affect the safety evaluation.
6. Inability to follow the study protocol for treatment or follow up as scheduled.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chen Xiaoping

OTHER

Sponsor Role lead

Responsible Party

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Chen Xiaoping

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Huapeng Sun

Xiangyang, Hubei, China

Site Status RECRUITING

Enyu Liu

Jinan, Shandong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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WanGuang Zhang

Role: CONTACT

13886195965

xiaoping Chen

Role: CONTACT

027-83663400

Facility Contacts

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Huapeng Sun

Role: primary

Enyu Liu

Role: primary

Other Identifiers

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Neoadj-Net01

Identifier Type: -

Identifier Source: org_study_id

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