Application of mRNA Immunotherapy Technology in Hepatitis B Virus-related Refractory Hepatocellular Carcinoma
NCT ID: NCT05738447
Last Updated: 2023-02-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE1
9 participants
INTERVENTIONAL
2023-02-15
2025-01-01
Brief Summary
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Detailed Description
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The mRNA vaccines are a highly promising novel anti-tumor approach. The applicant team of this project has carried out research on raw materials and preparation process, vaccine stability, quality standard, delivery vector construction, and anti-tumor mechanism of action of mRNA immune formulation in the early stage. Now we have completed the optimized design of mRNA raw materials, and the construction and optimization of the mRNA delivery vector. The tumor therapeutic mRNA immune formulation with high efficiency, safety, scalable preparation, and quality control has been selected and preclinical evaluation has been completed to verify its safety and efficacy. The project has constructed mRNA vaccines, and no similar therapeutic method or product has been reported in the international arena.
This project proposes to conduct a phase I clinical study based on the previous study to include patients with advanced hepatocellular carcinoma who have failed second-line standard treatment or cannot receive standard treatment. A dose-escalation trial will be conducted, and one effective dose will be selected for a fixed-dose trial to explore the safety, tolerability, and efficacy of mRNA immunotherapy technology for clinical application. Project implementation is expected to benefit a wide range of hepatocellular carcinoma patients and improve their prognosis.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment Cohort
With 20ug as the starting point, the dose was increased using a dose escalation scheme. Each subject only received one corresponding dose, and the intramuscular injection was administered again every 7 days, and after 4 doses, the 5th dose was given after 1-month interval.
HBV mRNA vaccine
With 20ug as the starting point, the dose was increased using a dose escalation scheme. Each subject only received one corresponding dose, and the intramuscular injection was administered again every 7 days, and after 4 doses, the 5th dose was given after 1-month interval.
Interventions
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HBV mRNA vaccine
With 20ug as the starting point, the dose was increased using a dose escalation scheme. Each subject only received one corresponding dose, and the intramuscular injection was administered again every 7 days, and after 4 doses, the 5th dose was given after 1-month interval.
Eligibility Criteria
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Inclusion Criteria
2. Patients with HBV-positive advanced hepatocellular carcinoma after failure of second-line standard therapy (including PD-1 inhibitor therapy, chemotherapy, and anti-vascular targeted drugs);
3. HBsAg positive, regardless of whether the peripheral blood is positive for HBV DNA.
4. ECOG physical fitness score: 0\~1 points;
5. Estimated survival ≥ 3 months;
6. The main organs have good function, that is, the relevant examination indicators within random 14 days meet the following requirements:
1. Blood routine examination: hemoglobin ≥ 80 g/L (no blood transfusion within 14 days); Neutrophil count\> 1.5×109/L; Platelet count≥ 80×109/L;
2. Biochemical examination: total bilirubin ≤ 1.5× ULN (upper limit of normal); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5×ULN; If liver metastases are present, ALT or AST ≤ 5×ULN; Endogenous creatinine clearance
≥ 60 ml/min (Cockcroft-Gault formula);
3. Cardiac Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥50%.
7. Sign the informed consent form;
8. Good compliance, family members agree to cooperate with survival follow-up.
Exclusion Criteria
2. The patient has a history of other tumors, unless it is cervical cancer in situ, treated cutaneous squamous cell carcinoma or bladder epithelial tumor or other malignant tumors that has received radical treatment (at least 5 years before enrollment)
3. Patients with uncontrolled cardiac clinical symptoms or diseases, such as heart failure above NYHA grade 2, unstable angina, myocardial infarction within 1 year, and clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
4. For female subjects: pregnant or lactating women.
5. The patient has active tuberculosis, bacterial or fungal infection (≥ grade 2 of NCI-CTC, 3rd edition); There is HIV infection with active HBV infection, HCV infection.
6. Those who have a history of psychotropic drug abuse and have mental disorders that cannot be remitted;
7. The subject has any active autoimmune disease or has a history of autoimmune disease (such as, but not limited to uveitis, enteritis, pituitary inflammation, nephritis, hyperthyroidism, hypothyroidism; Participants with vitiligo or who had complete remission of asthma in childhood and did not require any intervention in adulthood could be included; Participants in asthma requiring medical intervention with bronchodilators omitted).
8. According to the judgment of the investigator, there are concomitant diseases that seriously endanger the safety of patients or affect the completion of the patient's research.
18 Years
70 Years
ALL
Yes
Sponsors
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West China Hospital
OTHER
Responsible Party
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Xingchen Peng
Professor
Principal Investigators
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Xingchen Peng
Role: PRINCIPAL_INVESTIGATOR
West China Hospital
Locations
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West China Hospital, Sichuan University
Chengdu, Sichuan, China
Countries
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Central Contacts
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Facility Contacts
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References
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Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004 Jul;130(7):417-22. doi: 10.1007/s00432-004-0552-0.
Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004 Mar 11;350(11):1118-29. doi: 10.1056/NEJMra031087. No abstract available.
Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006 Jun 15;118(12):3030-44. doi: 10.1002/ijc.21731.
Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013 Jul;47 Suppl(0):S2-6. doi: 10.1097/MCG.0b013e3182872f29.
Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, Liang DC, Shau WY, Chen DS. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med. 1997 Jun 26;336(26):1855-9. doi: 10.1056/NEJM199706263362602.
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Nishikawa J, Yoshiyama H, Iizasa H, Kanehiro Y, Nakamura M, Nishimura J, Saito M, Okamoto T, Sakai K, Suehiro Y, Yamasaki T, Oga A, Yanai H, Sakaida I. Epstein-barr virus in gastric carcinoma. Cancers (Basel). 2014 Nov 7;6(4):2259-74. doi: 10.3390/cancers6042259.
Reinhard K, Rengstl B, Oehm P, Michel K, Billmeier A, Hayduk N, Klein O, Kuna K, Ouchan Y, Woll S, Christ E, Weber D, Suchan M, Bukur T, Birtel M, Jahndel V, Mroz K, Hobohm K, Kranz L, Diken M, Kuhlcke K, Tureci O, Sahin U. An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors. Science. 2020 Jan 24;367(6476):446-453. doi: 10.1126/science.aay5967. Epub 2020 Jan 2.
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Other Identifiers
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2022-1371
Identifier Type: -
Identifier Source: org_study_id
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