Clinical trial NCT04974281: PD-1 Antibody and Lenvatinib Plus TACE on Downstaging BCLC B/C HCC
Official title: Efficacy and Safety of PD-1 Antibody and Lenvatinib Plus TACE on Downstaging Hepatocellular Carcinoma With BCLC B/C
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Hepatocellular Carcinoma
Keywords: Lenvatinib
PD-1
TACE
Downstaging
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2021-07-23
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Resection rate
timeFrame: 6 months after downstaging treatment
Secondary outcomes:
measure: Adverse events (safety)
timeFrame: 6 months
measure: Overall survival (OS)
timeFrame: 2 years
measure: Objective response rate (ORR)
timeFrame: 6 months
measure: Progression free survival (PFS)
timeFrame: 6 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan hospital
state: Shanghai
Study officials:
affiliation: Department of Surgery, Huashan Hospital, Fudan University
name: Lunxiu Qin, M.D
role: STUDY_DIRECTOR
References:
citation: 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.
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.
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.
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.
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.