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

HCC Clinical Trial

Official title:

Efficacy and Safety of Neoadjuvant HAIC Combined With Tislelizumab and Lenvatinib in Patients With Resectable HCC Screened by a Multimodal Deep Learning Model: a Multicenter Randomized Controlled Trial.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06420440
• Other study ID #: Neoadj-Net01
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 1, 2024
• Est. completion date: May 31, 2027

Study information

• Verified date: May 2024
• Source: Tongji Hospital
• Contact: WanGuang Zhang
• Phone: 13886195965
• Email: wgzhang[@]tjh.tjmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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, there is no consensus on surgical treatment for patients with BCLC-stage B or C HCC. New tools are urgently needed to guide the choice of treatment options.

Description:

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, there is no consensus on surgical treatment for patients with BCLC-stage B or C HCC. Transarterial chemoembolization and systemic medication were the first line of treatment for this patients. In eastern countries, such as China, BCLC-B is further categorized into stages IIa and IIb, and surgical resection is recommended as the first-line treatment option for stage IIa, while surgical resection can also be considered for stage IIb. Moreover, many studies have found that patients with BCLC-C stage tumors can also benefit from surgery and the overall prognosis were better than non-surgical treatment. However, the rate of postoperative recurrence is higher than that of early HCC. 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.

Our 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 160
• Est. completion date: May 31, 2027
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 stage is BCLC B or C without distant metastasis, and is technically resectable.

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.

Related Conditions & MeSH terms

• HCC

Intervention

Procedure:
• 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)

Drug:
• 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).
• 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)

Procedure:
• 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.

Drug:
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Chen Xiaoping

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median event-free survival (EFS)	EFS is defined as the time from randomization to disease recurrence and/or disease progression or death from any cause.	From date of randomization until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 60 months.
Secondary	Safety Assessment	Any adverse event during treatment that is incompatible with the therapeutic purpose of the medication.The incidence and severity of adverse events and serious adverse events as assessed by CTCAE v5.0.	Baseline up to 12 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death from any cause	From date of randomization until the date of death from any cause, assessed up to 60 months.