Triple Therapy Sequential Radiotherapy in Unresectable HCC (TALENP003)

NCT ID: NCT06561399

Last Updated: 2024-08-20

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 28 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-08-15
• Study Completion Date: 2028-07-01

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.

Conditions

Hepatocellular Carcinoma Non-resectable

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Triple Therapy sequential Radiotherapy

TACE, Lenvatinib combination with Sintilimab sequential radiotherapy

Intervention Type: COMBINATION_PRODUCT

TACE, Lenvatinib \[8mg(\<60kg)/12mg(\>60kg) orally daily\] combination with Sintilimab (200mg administered intravenous injection on Day 1 of each 21-day cycle) for 2 months. Sequential radiotherapy method and dosage are comprehensively evaluated by radiologists, hepatobiliary surgeons, and oncologists, and discussed by a multidisciplinary team

Interventions

TACE, Lenvatinib combination with Sintilimab sequential radiotherapy

TACE, Lenvatinib \[8mg(\<60kg)/12mg(\>60kg) orally daily\] combination with Sintilimab (200mg administered intravenous injection on Day 1 of each 21-day cycle) for 2 months. Sequential radiotherapy method and dosage are comprehensively evaluated by radiologists, hepatobiliary surgeons, and oncologists, and discussed by a multidisciplinary team

Intervention Type: COMBINATION_PRODUCT

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fujian Provincial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Shao-Ming Wei

Department of Hepatobiliary Pancreatic Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shao-Ming Wei

Role: PRINCIPAL_INVESTIGATOR

Fujian Provincial Hospital

Locations

First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

Site Status: NOT_YET_RECRUITING

Fujian Provincial Hospital

Fuzhou, Fujian, China

Site Status: RECRUITING

Fujian provincial hospital

Fuzhou, Fujian, China

Site Status: NOT_YET_RECRUITING

Mengchao Hepatobiliary Hospital of Fujian Medical University

Fuzhou, Fujian, China

Site Status: NOT_YET_RECRUITING

Countries

China

Central Contacts

Shao-Ming Wei

Role: CONTACT

67468424@qq.com

(+86)13599037493

Facility Contacts

Zhi-Bo Zhang

Role: primary

zbzhang_1234@163.com

13960986516

Shao-Ming Wei

Role: primary

67468424@qq.com

(+86)13599037493

Mao-Lin Yan

Role: primary

yanmaolin74@163.com

0591-88217140

Yong-Yi Zeng

Role: primary

lamp197311@126.com

13805083802

Other Identifiers

TALENP003

Identifier Type: -

Identifier Source: org_study_id