Neoadjuvant IMRT Combined With Camrelizumab and Apatinib for Resectable HCC With PVTT

NCT06349317 | Recruiting Phase 2

• 1 other identifier: 2024-005
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, single-arm prospective clinical trial that evaluates the efficacy and safety of neoadjuvant intensity-modulated radiotherapy combined with perioperative camrelizumab and apatinib in the treatment of resectable hepatocellular carcinoma with portal vein tumor thrombus.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 1-year Event-Free Survival (EFS) rate

  EFS is defined as the time from the start of study treatment to the occurrence of tumor progression, relapse assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, death for any reason, or last follow-up (whichever occurs first).

  1 year

Secondary Outcomes (5)

• Event-Free Survival (EFS)

  up to 2 years

• Overall Survival (OS)

  up to 2 years

• Disease-Free Survival (DFS)

  up to 2 years

• R0 resection rate

  up to 3 months

• Overall Objective Response of primary liver tumor and PVTT

  up to 3 months

Other Outcomes (3)

• Surgical safety

  up to 3 months

• Safety of radiotherapy, camrelizumab and apatinib treatment

  up to 2 years

• Exploratory Endpoints

  up to 2 years

Study Arms (1)

Neoadjuvant intensity-modulated radiotherapy combined with perioperative camrelizumab and apatinib

EXPERIMENTAL

Neoadjuvant intensity-modulated radiotherapy combined with perioperative camrelizumab and apatinib

Combination Product: Neoadjuvant intensity-modulated radiotherapy combined with perioperative camrelizumab and apatinib

Interventions

Neoadjuvant intensity-modulated radiotherapy combined with perioperative camrelizumab and apatinib COMBINATION_PRODUCT

1. Preoperative IMRT targeting PVTT and intrahepatic tumor lesions with a prescribed dose for 18Gy in 6 fractions delivered by using 6-MV X-rays with a linear accelerator at 5 fractions per week; 2. Perioperative combination of camrelizumab and apatinib Preoperatively, camrelizumab (200mg, every 2 weeks) combined with apatinib (250mg, daily) for 2 cycles (2 weeks as one cycle); Postoperatively, camrelizumab (200mg, every 3 weeks) combined with apatinib (250mg, daily) for 8 cycles (3 weeks as one cycle).

Neoadjuvant intensity-modulated radiotherapy combined with perioperative camrelizumab and apatinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent and able to comply with scheduled visits and related procedures;
• Age ≥18 and ≤75 years, regardless of gender;
• Patients with HCC who meet the clinical diagnostic criteria of China's "Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma" (2022 Edition) or are diagnosed by biopsy, and have at least one measurable lesion according to the mRECIST criteria;
• Presence of portal vein tumor thrombus (PVTT) of Cheng's type I/II/III, with the primary tumor being resectable;
• Child-Pugh score of Class A;
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1;
• No prior antitumor treatment (such as surgery, radiotherapy, TACE, ablation, chemotherapy, targeted therapy, immunotherapy, or systemic therapy).
• For patients with hepatitis B virus (HBV) infection, testing for HBV-DNA is required; direct treatment initiation is allowed if HBV-DNA ≤2000 IU/mL; if HBV-DNA \>2000 IU/mL, antiviral therapy should be administered for one week before starting the treatment; all HBV positive patients will receive continuous antiviral treatment throughout the study; patients with hepatitis C virus (HCV) RNA positive must undergo antiviral treatment as per the guidelines;
• Participants must provide a fresh tumor biopsy sample during the screening period (can be waived after discussion with the medical monitor) and blood samples for monitoring immune cells, cytokine levels, and other relevant immune status in the tumor microenvironment;
• Expected survival of ≥12 weeks;
• Adequate organ and marrow function, as defined by the following laboratory values:
• Hematology: Absolute Neutrophil Count ≥1.5×109/L; Platelets ≥80×109/L; Hemoglobin ≥90g/L;
• Liver function: Total bilirubin ≤3× upper limit of normal (ULN); Alanine Aminotransferase and Aspartate Aminotransferase ≤5×ULN; Serum albumin ≥30g/L;
• Renal function: Serum creatinine (Cr) ≤1.5×ULN, or for patients with Cr \>1.5×ULN, creatinine clearance (CCr) ≥45 mL/min (Cockcroft-Gault formula); Urinalysis showing proteinuria \<2+; For participants with baseline proteinuria ≥2+, a 24-hour urine collection and quantitative protein \<1g is required;
• Coagulation: International Normalized Ratio or APTT ≤1.5×ULN;

You may not qualify if:

• PVTT located in the portal vein branch opposite the tumor, or with inferior vena cava tumor thrombus, extrahepatic metastasis, or tumor invasion of adjacent organs;
• Known intrahepatic cholangiocarcinoma, sarcomatoid HCC, mixed-cell carcinoma, and fibrolamellar carcinoma; active malignant tumors other than HCC within the past 5 years or concurrently, except for cured localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, and breast carcinoma in situ, which are allowed;
• Currently with interstitial pneumonia or interstitial lung disease, or history of interstitial lung disease requiring hormone treatment, or other conditions that may interfere with the judgement and management of immunotherapy-related pulmonary toxicity, such as pulmonary fibrosis, organizing pneumonia (e.g., obliterative bronchiolitis), pneumoconiosis, drug-related pneumonia, idiopathic pneumonia, or participants with active pneumonia or severe impairment of lung function shown on a chest CT during screening; active tuberculosis;
• Active autoimmune disease or history of autoimmune disease that may recur, including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (patients controllable with hormone replacement therapy are allowed); Patients with skin conditions that do not require systemic treatment, such as vitiligo, psoriasis, and alopecia, those with controlled Type I diabetes mellitus undergoing insulin therapy, or individuals whose childhood asthma has fully resolved with no need for intervention in adulthood, are allowed; patients requiring bronchodilators for medical intervention of asthma are not allowed;
• Use of immunosuppressive drugs or systemic corticosteroids for the purpose of immunosuppression (dose \>10mg/day of prednisone or equivalent) within 2 weeks before the start of the study;
• Active infection, fever of unknown origin ≥38.5°C within 1 week before the study start, or baseline white blood cell count \>15×10\^9/L; therapeutic antibiotics orally or intravenously within 2 weeks before the study start (excluding prophylactic antibiotics given IV for no more than 48 hours);
• Congenital or acquired immunodeficiency (e.g., HIV infection);
• Receipt of live attenuated vaccines within 4 weeks before the study start or expectation of needing such vaccines during the camrelizumab treatment period or within 60 days after the last dose of camrelizuma;
• Significant bleeding symptoms of clinical significance or a clear bleeding tendency within 6 months before the study start, such as gastrointestinal bleeding, hemorrhagic gastric ulcers, or vasculitis; if baseline fecal occult blood is positive, retesting is allowed, and if still positive, gastroduodenoscopy is required;
• Known genetic or acquired bleeding (e.g., coagulopathy) and thrombotic tendencies, such as hemophilia, coagulation mechanism disorders, thrombocytopenia, etc.; currently receiving full-dose oral or injectable anticoagulants or thrombolytic agents for therapeutic purposes (prophylactic use of low-dose aspirin, etc., is allowed);
• Arterial thromboembolic events within 6 months before the study start, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), CTCAE grade 3 or above deep vein thrombosis, pulmonary embolism, etc;
• Uncontrolled clinical symptoms or diseases of the heart, such as: (1) heart failure of NYHA class II or above or echocardiography showing LVEF \<50%; (2) unstable angina; (3) myocardial infarction within 1 year before treatment; (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; (5) QTc \> 450ms for males and \>470ms for females (QTc interval calculated using the Fridericia formula; if QTc is abnormal, continuous testing three times at 2-minute intervals is allowed, taking the average value);
• Hypertension not well controlled with antihypertensive medication (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg based on the average of ≥2 blood pressure readings), allowing achievement of the above parameters through antihypertensive treatment; history of hypertensive crisis or hypertensive encephalopathy;
• Major vascular diseases within 6 months before the study start (e.g., requiring surgical repair or recent peripheral arterial thrombosis of an aneurysm);
• Severe, unhealed, or open wounds and active ulcers or untreated fractures;

Sponsors & Collaborators

• Yongyi Zeng: lead

Study Sites (1)

Mengchao Hepatobiliary Hospital, Fujian Medical University

Fuzhou, Fujian, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

apatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Yongyi Zeng, Professor

  Meng Chao Hepatobiliary Hospital of Fujian Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yongyi Zeng, Professor

CONTACT

0591-88112620; lamp197311@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: March 31, 2024
• First Posted: April 5, 2024
• Study Start: April 22, 2024
• Primary Completion: May 1, 2026
• Study Completion: June 1, 2026
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)