PD-1 Antibody and Lenvatinib Plus TACE on Downstaging BCLC B/C HCC

Hepatocellular Carcinoma Clinical Trial

Official title:

Efficacy and Safety of PD-1 Antibody and Lenvatinib Plus TACE on Downstaging Hepatocellular Carcinoma With BCLC B/C

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04974281
• Other study ID #: HUASHAN007
• Status: Recruiting
• Phase: Early Phase 1
• Start date: January 1, 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: August 2022
• Source: Fudan University
• Contact: Lunxiu Qin, M.D
• Phone: +862152887172
• Email: qinlx99[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the difference of safety and efficacy about PD-1 Antibody and Lenvatinib Plus transcatheter arterial chemoembolization (TACE) on downstaging hepatocellular carcinoma with BCLC B/C.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age =18 years old and =75 years old;

2. Clinically diagnosed as hepatocellular carcinoma, stage B/C of BCLC;

3. No history of severe arrhythmia or heart failure;

4. No history of severe ventilation dysfunction or severe pulmonary infection;

5. No acute or chronic renal failure, the creatinine clearance rate was >40 mL/min;

6. Liver function Child A;

7. Blood routine: absolute neutrophils count =1.5×10^9/L, Hb=8.5g/L, PLT=75×10^9/L;

8. Coagulation function: INR=2.3;

9. ECOG score <2;

10. No local or systemic treatment, such as TACE, RFA, targeted drugs, traditional Chinese medicine, etc., before enrollment;

11. Expected survival =12 weeks;

12. At least one lesion can be measured and evaluated by CT/MRI according to RECIST 1.1 criteria;

13. Understand and sign the informed consent.

Exclusion Criteria:

1. Pregnant or lactating women;

2. Patients with other malignant tumors;

3. patients with complicated mental illness;

4. patients who have participated in other clinical trials in the last three months;

5. known or suspected allergy to any drug related to the study;

6. Patients with positive immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)

7. Patients treated with other targeted drugs, PD-L1 antibody and other immunotherapy or FOLFOX systemic chemotherapy after inclusion;

8. Patients with =1 + proteinuria indicated by urine routine will receive 24-hour urine protein detection, and patients with =1g 24-hour urine protein will not be included in the group.

9. Active autoimmune diseases that require systemic treatment (use of disease-alleviating agents, such as corticosteroids or immunosuppressants)

10. Patients with uncontrolled hepatitis B/C infection

11. Other conditions that the researcher considers not suitable for inclusion in this study

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Combination Product:
• PD-1 and Lenvatinib Plus TACE
PD-1 Antibody and Lenvatinib Plus Transarterial chemoembolization(TACE ): Patients were recommended to receive TACE once every 6 weeks. Patients were recommended to begin oral administration of Lenvatinib 3 days after the first TACE treatment, and meanwhile to start intravenous drip of PD-1 antibody 3 days after the first TACE treatment, once every 3 weeks.

Locations

Country	Name	City	State
China	Huashan hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

References & Publications (5)

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum in: CA Cancer J Clin. 2020 Jul;70(4):313. — View Citation

Kato Y, Tabata K, Kimura T, Yachie-Kinoshita A, Ozawa Y, Yamada K, Ito J, Tachino S, Hori Y, Matsuki M, Matsuoka Y, Ghosh S, Kitano H, Nomoto K, Matsui J, Funahashi Y. Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8+ T cells through reduction of tumor-associated macrophage and activation of the interferon pathway. PLoS One. 2019 Feb 27;14(2):e0212513. doi: 10.1371/journal.pone.0212513. eCollection 2019. — View Citation

Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1. — View Citation

Kudo M, Ueshima K, Ikeda M, Torimura T, Tanabe N, Aikata H, Izumi N, Yamasaki T, Nojiri S, Hino K, Tsumura H, Kuzuya T, Isoda N, Yasui K, Aino H, Ido A, Kawabe N, Nakao K, Wada Y, Yokosuka O, Yoshimura K, Okusaka T, Furuse J, Kokudo N, Okita K, Johnson PJ, Arai Y; TACTICS study group. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial. Gut. 2020 Aug;69(8):1492-1501. doi: 10.1136/gutjnl-2019-318934. Epub 2019 Dec 4. — View Citation

Lencioni R, de Baere T, Soulen MC, Rilling WS, Geschwind JF. Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data. Hepatology. 2016 Jul;64(1):106-16. doi: 10.1002/hep.28453. Epub 2016 Mar 7. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Resection rate	Resction rate refers to the proportion of patients who can receive radical surgery after downstaging treatment.	6 months after downstaging treatment
Secondary	Adverse events (safety)	Postoperative adverse events (safety ) will be evaluated according to the NCI CTCAE Version 4.03.The number and severity of treatment-related side effects, including AE and SAE, will be recorded during treatment.	6 months
Secondary	Overall survival (OS)	The duration from the date of recruitment to the date of death from any cause.	2 years
Secondary	Objective response rate (ORR)	ORR is defined as the percentage of participants who have a confirmed complete response or partial response according to RECIST 1.1 or mRECIST.	6 months
Secondary	Progression free survival (PFS)	PFS is defined as the time from enrollment of the trial to the first documented disease progression or death due to any cause.	6 months