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NCT Number: NCT06524466

Neoadjuvant SBRT Combined With Lenvatinib and Pucotenlimab for Resectable Hepatocellular Carcinoma

At the time of diagnosis, the majority of hepatocellular carcinoma (HCC) patients are at the intermediate to advanced stages, with a 50-70% incidence of macrovascular invasion (including portal vein, hepatic vein, inferior vena cava, or bile duct invasion). Tyrosine kinase inhibitors (TKI, including lenvatinib and sorafenib) or a combination of TKIs and immune therapy is one of the standard treatment options recommended by HCC guidelines. However, numerous retrospective studies have reported that for surgically resectable HCC with macrovascular invasion, surgical resection yields better efficacy than non-surgical treatments (including transarterial interventional therapies and/or systemic therapies). Nevertheless, the postoperative recurrence rate remains exceedingly high, exceeding 80%. Therefore, determining comprehensive approaches to enhance surgical radicality and reduce postoperative recurrence rates is a current research hotspot.

Recent studies have found that neoadjuvant therapy (including immunotherapy alone or in combination with TKI) before surgery can reduce postoperative recurrence rates and extend survival rates. Moreover, SBRT combined with TKI and immunotherapy has a sensitizing effect, particularly showing good sensitivity and control rates for vascular invasion.

Thus, this study aims to conduct a prospective, single-arm phase II clinical trial targeting patients with surgically resectable HCC with macrovascular invasion. The primary endpoints are objective response rate (ORR) and treatment completion rate, to evaluate the efficacy and safety of the preoperative neoadjuvant therapy with the combination of SBRT, lenvatinib, and pucotenlimab (an anti PD-1 drug). The secondary endpoints include progression-free survival (PFS), overall survival (OS), incidence of adverse events, pathological response rate, and incidence of surgical complications, to preliminarily evaluate the efficacy of the neoadjuvant therapy with this triple regimen.

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Key information

Conditions

Resectable Hepatocellular Carcinoma CNLC IIIA Stage Macrovascular Invasion

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • All patients must be pathologically confirmed to have hepatocellular carcinoma by biopsy；
  • No previous antitumor treatment;
  • Tumor number ≤ 3, diameter ≤ 10 cm, confined to one lobe of the liver or the middle lobe, evaluated by a surgeon as resectable;
  • Combined with vascular invasion, with the following extents: unilateral portal vein invasion without extending beyond the main portal vein; hepatic vein invasion not reaching the inferior vena cava; unilateral bile duct invasion not reaching the common hepatic duct;
  • No extra-hepatic metastasis or lymph node metastasis.
  • Normal liver volume ≥ 700 cc;
  • Patient KPS ≥ 90;
  • Liver function Child-Pugh class A;
  • Estimated survival of more than 6 months;
  • Function of important organs meets the following requirements: white blood cells ≥ 4.0×10^9/l, neutrophils ≥ 1.5×10^9/l, platelets ≥ 80.0×10^9/l, hemoglobin ≥ 90 g/l; serum albumin ≥ 2.8 g/dl; total bilirubin ≤ 1.5× ULN, ALT/AST/ALP ≤ 2.5 × ULN; serum creatinine ≤ 1.5 × ULN or creatinine clearance rate > 60 mL/min; no severe organic diseases;
  • The subject must be able to understand and voluntarily sign a written informed consent form, and must sign the informed consent form prior to any specific procedure of the study, agreeing to comply with the medication and postoperative follow-up requirements as designed in this study.

Exclusion criteria

  • Combined with severe impairment of functions of other important organs such as heart, lungs, and kidneys; active infections other than viral hepatitis or other serious comorbid conditions, making the patient unable to tolerate treatment;
  • Diffuse type of HCC, or tumor volume exceeding 50% of liver volume;
  • Portal vein invasion extending beyond the main tract of the portal vein, or hepatic vein invasion reaching the inferior vena cava, or bile duct invasion extending beyond the common hepatic duct;
  • Contraindications to surgical resection, SBRT and immunotherapy;
  • History of other malignant tumors;
  • Combined with immunological diseases or other conditions requiring long-term steroid treatment;
  • Known or suspected allergy to the study drug or any drugs administered in connection with this trial;
  • History of organ transplantation;
  • Pregnant or breastfeeding women;
  • Other factors that may affect patient enrollment and assessment outcomes;
  • Refusal to follow-up according to the requirements set by the study protocol, and refusal to sign the informed consent form.

Treatment and study plan

Neoadjuvant SBRT combined with Lenvatinib and Pucotenlimab

Drug

SBRT: SBRT will be performed within 2-4 weeks after enrollment. The total radiation dose will be 24 Gy, delivered in 3 fractions on alternate days, to be completed within one week.

Lenvatinib: 8mg/day, begin immediately after enrollment. Lenvatinib should be discontinued one week before surgery.

Pucotenlimab: 200mg，3-week interval between cycles, begin immediately after enrollment, a total of four cycles of Puco treatment must be completed before surgery.

Surgical resection will be performed within 10-16 weeks after the completion of SBRT.

Primary outcomes

  1. objective response rate (ORR)

    Time frame: From date of neoadjuvant treatment beginning until the date of neoadjuvant treatment completion, up to 1 year.

    The ratio of patients achieving the best efficacy of neoadjuvant therapy, including complete response (CR) and partial response (PR), to all patients.

  2. treatment complete rate (TCR)

    Time frame: From date of neoadjuvant treatment beginning until the date of neoadjuvant treatment completion, up to 1 year.

    The ratio of patients completing the neoadjuvant therapy to all patients.

Secondary outcomes

  1. progression-free survival (PFS)

    Time frame: From date of neoadjuvant treatment beginning until the date of follow-up completion, up to 2 year.

    PFS is defined as the time from treatment to the first confirmed disease progression. For patients who undergo surgical resection, disease progression is defined as postoperative recurrence/metastasis. For patients who do not undergo surgical resection, disease progression is confirmed based on imaging assessment according to the mRECIST criteria.

  2. overall survival (OS)

    Time frame: From date of neoadjuvant treatment beginning until the date of death from any cause, assessed up to 2 years.

    OS is defined as the time from randomization to death from any cause

  3. incidence of adverse events (safety )

    Time frame: From date of neoadjuvant treatment beginning until 3 months after treatment completion, up to 1 year.

    Treatment-related adverse events are evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE 5.0).

  4. perioperative complication rate

    Time frame: The period from the start of surgery to the patient's discharge from hospital, up to 1 year.

    Perioperative complication includes intraoperative complications such as bleeding and transfusion, extensive adhesions, diaphragm resection, prolonged surgery time, etc., as well as postoperative complications such as bleeding, infection, bile leakage, liver dysfunction, etc.

  5. pathological complete response (pCR)

    Time frame: From date of neoadjuvant treatment beginning until the date of surgical resection completion, up to 1 year.

    The ratio of patients with no viable tumor cells in the pathology after resection to all patients undergoing surgical resection.

Sponsors and collaborators

Lead sponsor

Sun Yat-sen University

Other

Registry information

Official study title

Neoadjuvant Stereotactic Body Radiotherapy (SBRT) Combined With Lenvatinib and Pucotenlimab for Resectable Hepatocellular Carcinoma With Macrovascular Invasion: A Single-arm, Phase II Study

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Jul 29, 2024
Registry last updated
Jul 29, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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