Clinical trial NCT06569498: Neoadjuvant Triple Therapy for Resectable HCC
Official title: Neoadjuvant Transcatheter Arterial Chemoembolization Combined With Lenvatinib Plus Cadonilimab for Resectable Hepatocellular Carcinoma: A Single-Arm Phase II Clinical Trial
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Resectable Hepatocellular Carcinoma
Lead sponsor: Fujian Provincial Hospital
Sponsor class: OTHER
First posted: 2024-08-26
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with hepatocellular carcinoma being treated at Fujian Provincial Hospital or other centers participating in this study

Brief summary: This study is a single-arm, multi-center, prospective phase II trial aimed at evaluating the efficacy and safety of neoadjuvant therapy with transarterial chemoembolization (TACE) combined with lenvatinib and camrelizumab (triple therapy) in patients with resectable hepatocellular carcinoma (HCC). The study plans to enroll 20 patients. The primary endpoints are major pathological response (MPR) rate and safety, while the secondary endpoints are recurrence-free survival (RFS), objective response rate (ORR), R0 resection rate, and overall survival (OS).


Eligibility criteria: Inclusion Criteria:

1. Voluntarily join the study and sign the informed consent form.
2. Male or female patients aged between 18 and 75 years.
3. Child-Pugh class A.
4. Indocyanine green 15-minute retention rate (ICGR-15) \< 15%.
5. ECOG performance status 0-1.
6. Diagnosed with hepatocellular carcinoma (HCC) according to the "Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2022 Edition)."
7. BCLC stage A or B, with a single tumor larger than 5 cm or multiple tumors, and considered surgically resectable after multidisciplinary discussion.
8. According to RECIST 1.1 criteria, the patient has at least one measurable lesion (a measurable lesion with a long diameter ≥ 10 mm on CT/MRI scan, and the measurable lesion has not received local treatments such as radiotherapy or cryotherapy).
9. Blood routine: absolute neutrophil count ≥ 1.5 × 10\^9/L, Hb ≥ 8.5 g/L, PLT ≥ 75 × 10\^9/L.
10. No history of severe arrhythmia, heart failure, severe pulmonary ventilation disorders, or severe lung infections; no acute or chronic renal failure, and creatinine clearance rate \> 40 mL/min.
11. Women of childbearing potential must agree to use contraception during the medication period and for 6 months after the end of medication; have a negative serum or urine pregnancy test within 7 days prior to enrollment, and must not be breastfeeding. Men must agree to use contraception during the study period and for 6 months after the end of the study.

Exclusion Criteria:

1. Tumor rupture with bleeding or suspected abdominal cavity metastasis.
2. Previous treatment with any antitumor therapies before enrollment, such as targeted drugs, PD-1/PD-L1/CTLA-4 monoclonal antibodies, surgery, TACE, FOLFOX systemic chemotherapy, radiotherapy, and Huaier granules.
3. History of allergy to lenvatinib, cadonilimab, or their components.
4. Presence of any active autoimmune disease or a history of autoimmune disease with expected recurrence (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases and syndromes); hypothyroidism treated with stable doses of thyroid replacement hormone; type 1 diabetes mellitus treated with stable doses of insulin; excluding patients with vitiligo or childhood asthma/allergies that have resolved and require no intervention in adulthood.
5. History of immunodeficiency; patients using immunosuppressive drugs or systemic corticosteroids for immunosuppressive purposes and who have continued using them within 2 weeks before signing the informed consent form.
6. Known hereditary or acquired bleeding (e.g., coagulopathy) or thrombotic tendency, such as hemophilia; currently receiving or recently (within 10 days before the start of study treatment) receiving full-dose oral or injectable anticoagulants or thrombolytics for therapeutic purposes (prophylactic use of low-dose aspirin and low-molecular-weight heparin is allowed).
7. Severe infection within 4 weeks before the first use of the study drug (CTC AE grade \> 2), such as severe pneumonia requiring hospitalization, bacteremia, or infection complications; baseline chest imaging indicating active lung inflammation; symptoms and signs of infection within 2 weeks before the first use of the study drug or requiring oral or intravenous antibiotic treatment (excluding prophylactic antibiotic use).
8. Urinalysis indicating proteinuria ≥ 1+; if so, a 24-hour urine protein test is required; patients with 24-hour urine protein ≥ 1 g.
9. History of other malignancies within the past 5 years or concurrently, except for cured basal cell carcinoma of the skin, cervical carcinoma in situ, and papillary thyroid carcinoma.
10. Patients with concomitant psychiatric disorders; history of substance abuse, alcohol, or drug addiction.
11. Pregnant or breastfeeding women.
12. Patients with significant surgical contraindications, such as renal and cardiopulmonary insufficiency, as judged by the investigator, or any other reasons deemed unsuitable for participation in this trial by the investigator.

Primary outcomes:
measure: MPR rate
timeFrame: Immediately after surgery
measure: Adverse events
timeFrame: From the initiation of medication, with recordings made whenever an adverse reaction occurs, assessed up to 12 months.
measure: Operative mortality
timeFrame: From date of surgery, assessed up to 1 month.
measure: Operative complications
timeFrame: From date of surgery, assessed up to 12 months.
measure: Reoperation rate
timeFrame: From date of surgery, assessed up to 12 months.
Secondary outcomes:
measure: RFS
timeFrame: From date of surgery until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 60 months.
measure: ORR
timeFrame: Four weeks after the initiation of medication until the day before surgery
measure: R0 resection rate
timeFrame: Immediately after surgery
measure: OS
timeFrame: From date of surgery until the date of death from any cause, assessed up to 60 months.
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fujian provincial hospital
state: Fujian
city: Fuzhou
country: China
facility: First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary Hospital of Fujian Medical University
state: Fujian
city: Xiamen
country: China
facility: Zhongshan Hospital of Xiamen University
state: Fujian
city: Xiamen
country: China
facility: First Affiliated Hospital of Xiamen University
state: Fujian
city: Zhangzhou
country: China
facility: Zhangzhou Affiliated Hospital of Fujian Medical University
state: Fujian
Study officials:
References: