Triple therapy for patients with unresectable liver cancer

A Single-arm, Phase II, Prospective Study of Transcatheter Arterial Chemoembolization, Lenvatinib Combination With Sintilimab Sequential Radiotherapy in Patients With Initial Unresectable Hepatocellular Carcinoma

This study is testing a new combination treatment for patients with hard-to-treat liver cancer to see if it can help shrink tumors more and improve survival rates.

Quick facts

• Study type: Observational
• Enrollment: 28 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fujian Provincial Hospital (Academic / other)
• Drugs / interventions: Sintilimab, Lenvatinib, chemotherapy, immunotherapy, radiation
• Locations: 4 sites (Fuzhou, Fujian and 3 other locations)
• Trial ID: NCT06561399 on ClinicalTrials.gov

What this trial studies

This observational study evaluates the efficacy and safety of a combination treatment involving Transcatheter arterial chemoembolization (TACE), Lenvatinib, and Sintilimab, followed by sequential radiotherapy in patients with unresectable hepatocellular carcinoma (uHCC). The goal is to achieve deeper tumor remission and improve long-term survival rates for patients who have not reached complete response after initial treatment. The study is multicenter and prospective, focusing on patients with specific eligibility criteria, including those with partial response or stable disease after prior treatment. By assessing the outcomes of this triple therapy approach, the study aims to enhance oncological results for uHCC patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with unresectable hepatocellular carcinoma who have shown partial response or stable disease after initial treatment.

Not a fit: Patients with Child-Pugh class B or C liver function, or those with a diagnosis of hepatocellular carcinoma not meeting the study's specific criteria, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved tumor remission and longer survival rates for patients with unresectable liver cancer.

How similar studies have performed: While this approach combines established treatments, the specific sequential use of these therapies in this context is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Be willing and able to enrollment in this study, signing the informed consent form;
2. Age between 18 and 75 years old, male or female patients;
3. Child-Pugh class A;
4. Indocyanine green 15 min retention rate (ICGR-15) \<15%;
5. ECOG score 0-1;
6. Diagnosis of hepatocellular carcinoma according to the Chinese HCC Diagnosis and Treatment Guidelines 2022 Edition and expected survival time greater than 4 months.
7. Patients with a diagnosis of initial unresectable HCC (BCLC stage B or C), evaluated as partial response (PR) or stable disease (SD) by RECIST 1.1 after 2 months of treatment with TACE, Lenvatinib combination with Sintilimab. The number of residual active lesions in the liver was 1 to 3 and suitable for radiation therapy. Fusion lesions in the liver were considered as 1 lesion, and portal vein cancer thrombus was considered as 1 lesion for treatment.
8. Normal tissue limits were performed according to the UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy.
9. Patients who have not received any tumor-related targeted, immunotherapy, radiotherapy and chemotherapy before enrollment;
10. Patients with at least one measurable lesion according to RECIST 1.1 criteria (measurable lesion CT/MRI scan length diameter ≥10mm, and measurable lesion has not received localized treatments such as radiotherapy, cryotherapy, etc.);
11. Blood routine: absolute neutrophil count ≥1.5×10\^9/L, Hb ≥8.5g/L, PLT ≥75×10\^9/L;
12. No history of severe cardiac arrhythmia or heart failure; no history of severe ventilatory dysfunction or severe pulmonary infection; no acute or chronic renal failure with creatinine clearance \>40 mL/min;
13. Women of childbearing age should agree that they must use contraception during and for 6 months after the end of the dosing period; patients who have had a negative serum or urine pregnancy test within 7 days prior to study enrollment and must be non-lactating, and men should agree that they must use contraception during and for 6 months after the end of the study period.

Exclusion Criteria:

1. Patients with a diagnosis of initial unresectable HCC, assessed as complete response (CR) or Progressive disease (PD) by RECIST 1.1 after 2 months of treatment with TACE, Lenvatinib combined with Sintilimab;
2. Tumor combined with cancerous thrombus in the inferior vena cava and the tumor has developed extrahepatic metastasis;
3. Treatment with other antitumor therapy such as targeted drugs, PD-1/PD-L1 inhibitors, surgery, TACE, radiotherapy, FOLFOX systemic chemotherapy, and locus coeruleus granule drugs prior to study entry;
4. History of allergy to Lenvatinib, Sintilimab and their components;
5. Tumor volume accounting for two-thirds or more of the liver volume or diffuse distribution of intrahepatic lesions;
6. Presence of any active autoimmune disease or patients with autoimmune disease with expected relapse (e.g., interstitial pneumonitis, colitis, hepatitis, pituitary gland inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including, but not limited to, these disorders and syndromes); hypothyroidism treated with stabilized doses of thyroid-replacing hormone; 1-year old diabetes mellitus using stabilized doses of insulin; or Type 1 diabetes mellitus; but not vitiligo or resolved childhood asthma/allergies that do not require any intervention in adulthood;
7. Patients have history of immunodeficiency; patients who are on immunosuppressive or systemic hormone therapy for immunosuppression and have continued to do so within 2 weeks prior to signing the informed consent form
8. Have known hereditary or acquired bleeding (e.g., coagulation disorders) or thrombotic tendencies, such as in patients with hemophilia; current or recent (within 10 days prior to initiation of study treatment) use of full-dose oral or injectable anticoagulant or thrombolytic medications for therapeutic purposes (prophylactic use of low-dose aspirin, low-molecular heparin is permitted)
9. Severe infections (CTCAE \> Grade 2) such as severe pneumonia requiring hospitalization, bacteremia, or infectious co-morbidities within 4 weeks prior to the first dose of study drug; baseline chest imaging suggestive of active lung inflammation, signs and symptoms of infection within 2 weeks prior to the first dose of study drug, or requiring treatment with oral or intravenous antibiotics (excluding prophylactic antibiotics). (excluding prophylactic use of antibiotics);
10. Patients with proteinuria with routine urinalysis suggestive of ≥ 1 + will undergo a 24-hour urine protein test for 24-hour urine protein ≥ 1g;
11. Have history of other malignant tumors within the previous 5 years or concurrently, except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix and papillary thyroid carcinoma;
12. Patients with co-morbid mental diseases; history of psychotropic substance abuse, alcoholism and drug addiction;
13. Women who are pregnant or breastfeeding
14. Patients with obvious contraindications to surgery, such as renal and cardiopulmonary insufficiency, as judged by the investigator, and those who, in the opinion of the investigator, should not participate in this trial for other reasons.

Where this trial is running

Fuzhou, Fujian and 3 other locations

• First Affiliated Hospital of Fujian Medical University — Fuzhou, Fujian, China (Not_yet_recruiting)
• Fujian Provincial Hospital — Fuzhou, Fujian, China (Recruiting)
• Fujian provincial hospital — Fuzhou, Fujian, China (Not_yet_recruiting)
• Mengchao Hepatobiliary Hospital of Fujian Medical University — Fuzhou, Fujian, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Shao-Ming Wei — Fujian Provincial Hospital
• Study coordinator: Shao-Ming Wei

Conditions Hepatocellular Carcinoma Non-resectable; Hepatocellular carcinoma; TACE; Lenvatinib; Sintilimab; radiotherapy