Clinical trial NCT06561399: Triple Therapy Sequential Radiotherapy in Unresectable HCC (TALENP003)
Official title: A Single-arm, Phase II, Prospective Study of Transcatheter Arterial Chemoembolization, Lenvatinib Combination With Sintilimab Sequential Radiotherapy in Patients With Initial Unresectable Hepatocellular Carcinoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatocellular Carcinoma Non-resectable
Keywords: Hepatocellular carcinoma
TACE
Lenvatinib
Sintilimab
radiotherapy
Lead sponsor: Fujian Provincial Hospital
Sponsor class: OTHER
First posted: 2024-08-20
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Unresectable Hepatocellular Carcinoma

Brief summary: This is an Open-label, Multicenter, Phase II clinical trial to evaluate the efficacy and safety of Transcatheter arterial chemoembolization (TACE), Lenvatinib combination with Sintilimab (Triple Therapy) sequential radiotherapy in patients with Unresectable Hepatocellular Carcinoma (uHCC).

Detailed description: For Unresectable Hepatocellular Carcinoma (uHCC) patients, Transcatheter arterial chemoembolization (TACE), Lenvatinib combined with PD-1 inhibitors treatment is an important choice, which can achieve deeper tumor remission. However, there are still some patients whose lesions have not reached complete response after treatment. According to research, patients with complete response of lesions after conversion therapy have a more ideal long-term survival rate. For populations that have not yet achieved complete response, sequential radiotherapy will achieve deeper tumor remission, delay recurrence, and achieve better oncological outcomes. This study is a single arm, multicenter, prospective clinical trial designed to evaluate the efficacy and safety of TACE, Lenvatinib combination with Sintilimab (Triple Therapy) sequential radiotherapy in the treatment of uHCC patients.

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.

Primary outcomes:
measure: Objective response rate, ORR
timeFrame: 4 weeks after the initiation of medication until the day before surgery
Secondary outcomes:
measure: Progression free survival, PFS
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
measure: Overall survival, OS
timeFrame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 60 months
measure: Objective response rate, ORR
timeFrame: 4 weeks after the initiation of medication until the day before surgery
measure: Conversion resection rate, CRR
timeFrame: 3 months
measure: Major pathological response rate, MPR rate
timeFrame: Immediately after surgery
measure: Toxicity Adverse events
timeFrame: through study completion, assessed up to 60 months
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Fuzhou
country: China
facility: Fujian Provincial Hospital
state: Fujian
city: Fuzhou
country: China
facility: Fujian provincial hospital
state: Fujian
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary Hospital of Fujian Medical University
state: Fujian
Study officials:
affiliation: Fujian Provincial Hospital
name: Shao-Ming Wei
role: PRINCIPAL_INVESTIGATOR
References: