Malignant Tumors Clinical Trial
Official title:
A Phase I Study of mRNA Vaccine for Patients With EBV-positive Advanced Malignant Tumors
The purpose of this study is to evaluate the efficacy and safety of mRNA vaccine for the EBV-positive Advanced Malignant Tumors.
Status | Recruiting |
Enrollment | 9 |
Est. completion date | January 2025 |
Est. primary completion date | January 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | Inclusion Criteria: 1. Male or female patients: =18 years old and =70 years old. 2. Patients with EBV-positive advanced malignant tumors after failure of second-line standard therapy. 3. ECOG physical condition score: 0-1 point. 4. Expected survival period = 3 months. 5. The main organs are in good function, that is, the relevant inspection indicators within 14 days before randomization meet the following requirements: 1. Blood routine examination: hemoglobin = 90g/L and neutrophil count > 1.5×109/L and platelet count = 80×109/L. 2. Biochemical examination: total bilirubin=1.5×ULN (upper limit of normal value), blood alanine aminotransferase (ALT) or blood aspartate aminotransferase (AST)=2.5×ULN. if there is liver metastasis, ALT or AST=5×ULN. Endogenous creatinine clearance = 60ml/min (Cockcroft-Gault formula). 3. Cardiac Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) = 50%. 6. Sign the written informed consent 1. Subjects must sign and date the EC-approved written informed consent in accordance with the guidelines of the competent authority and the research institution. Informed consent must be signed prior to any protocol-related procedures that are not part of the subject's routine medical care. 2. Subjects must be willing and able to comply with the scheduled visits, treatment plans, laboratory tests, and other requirements of the study. Exclusion Criteria: Patients who meet any of the following criteria cannot be enrolled: 1. Participated in other drug clinical trials within 4 weeks; 2. The patient has a history of other tumors, unless it is cervical cancer in situ, treated skin squamous cell carcinoma or bladder epithelial tumor or other malignant tumors that have received radical treatment (at least 5 years before enrollment); 3. There are clinical symptoms or diseases of the heart that cannot be well controlled, such as: heart failure above NYHA grade 2, unstable angina, myocardial infarction within 1 year, clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention of patients. 4. For female subjects: pregnant or lactating women. 5. Patients have active pulmonary tuberculosis, bacterial or fungal infection (=2 grades of NCI-CTCAE 5.0); HIV infection, active HBV infection, HCV infection. 6. Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders; 7. The subject has any active autoimmune disease or has a history of autoimmune disease (such as the following, but not limited to: uveitis, enteritis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; the subject suffers from Subjects with vitiligo or asthma that had been completely remitted in childhood and who did not require any intervention in adulthood could be included; subjects with asthma requiring medical intervention with bronchodilators could not be included). 8. Any abnormalities or permanent body art (such as tattoos) at the inoculation site that, in the opinion of the investigator, would prevent observation of local reactions at the inoculation site. 9. Patients who have been vaccinated with mRNA drugs. 10. Have participated in clinical trials involving lipid nanoparticles (one of the components of the vaccine in this study). 11. There are contraindications for intramuscular injection 12. History of drug abuse or known medical, psychological or social conditions, such as history of alcohol or drug abuse. 13. Known allergy, hypersensitivity or intolerance to the research vaccine (including any excipients). There is a history of severe allergy to any drug, food, or vaccination, such as anaphylactic shock, allergic laryngeal edema, allergic dyspnea, allergic purpura, thrombocytopenic purpura, local allergic necrotic reaction (Arthus reaction), etc. 14. From the screening period to 12 months after the full injection of the drug, the female subject has a pregnancy plan or the partner of a male subject has a pregnancy plan. 15. According to the investigator's judgment, there are concomitant diseases that seriously endanger the patient's safety or affect the patient's completion of the study. |
Country | Name | City | State |
---|---|---|---|
China | West China Hospital, Sichuan University | Chengdu | Sichuan |
Lead Sponsor | Collaborator |
---|---|
West China Hospital |
China,
Balfour HH Jr, Schmeling DO, Grimm-Geris JM. The promise of a prophylactic Epstein-Barr virus vaccine. Pediatr Res. 2020 Jan;87(2):345-352. doi: 10.1038/s41390-019-0591-5. Epub 2019 Oct 3. — View Citation
Chia WK, Wang WW, Teo M, Tai WM, Lim WT, Tan EH, Leong SS, Sun L, Chen JJ, Gottschalk S, Toh HC. A phase II study evaluating the safety and efficacy of an adenovirus-DeltaLMP1-LMP2 transduced dendritic cell vaccine in patients with advanced metastatic nasopharyngeal carcinoma. Ann Oncol. 2012 Apr;23(4):997-1005. doi: 10.1093/annonc/mdr341. Epub 2011 Aug 4. — View Citation
ERLAY J EM, LAM F, et al. Global Cancer Observatory: cancer today . Lyon, France: International Agency for Research on Cancer 2018 https://gcoiarcfr/today (accessed November 11th, 2020). 2018.
Fenton OS, Kauffman KJ, McClellan RL, Kaczmarek JC, Zeng MD, Andresen JL, Rhym LH, Heartlein MW, DeRosa F, Anderson DG. Customizable Lipid Nanoparticle Materials for the Delivery of siRNAs and mRNAs. Angew Chem Int Ed Engl. 2018 Oct 8;57(41):13582-13586. doi: 10.1002/anie.201809056. Epub 2018 Sep 14. — View Citation
Hou X, Zhang X, Zhao W, Zeng C, Deng B, McComb DW, Du S, Zhang C, Li W, Dong Y. Author Correction: Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis. Nat Nanotechnol. 2020 Jul;15(7):615. doi: 10.1038/s41565-020-0675-8. — View Citation
Hui EP, Taylor GS, Jia H, Ma BB, Chan SL, Ho R, Wong WL, Wilson S, Johnson BF, Edwards C, Stocken DD, Rickinson AB, Steven NM, Chan AT. Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients. Cancer Res. 2013 Mar 15;73(6):1676-88. doi: 10.1158/0008-5472.CAN-12-2448. Epub 2013 Jan 24. — View Citation
Iizasa H, Nanbo A, Nishikawa J, Jinushi M, Yoshiyama H. Epstein-Barr Virus (EBV)-associated gastric carcinoma. Viruses. 2012 Dec;4(12):3420-39. doi: 10.3390/v4123420. — View Citation
Miao L, Li L, Huang Y, Delcassian D, Chahal J, Han J, Shi Y, Sadtler K, Gao W, Lin J, Doloff JC, Langer R, Anderson DG. Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation. Nat Biotechnol. 2019 Oct;37(10):1174-1185. doi: 10.1038/s41587-019-0247-3. Epub 2019 Sep 30. — View Citation
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. — View Citation
Qiao YW, Zhao XQ, Liu J, Yang WJ. Clinicopathological features of Epstein-Barr virus-associated gastric carcinoma: A systematic review and meta-analysis. J BUON. 2019 May-Jun;24(3):1092-1099. — View Citation
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. — View Citation
Ribeiro J, Malta M, Galaghar A, Afonso LP, Libanio D, Medeiros R, Dinis-Ribeiro M, Pimentel-Nunes P, Sousa H. Epstein-Barr virus is absent in gastric superficial neoplastic lesions. Virchows Arch. 2019 Dec;475(6):757-762. doi: 10.1007/s00428-019-02670-1. Epub 2019 Nov 1. — View Citation
Saha A, Kaul R, Murakami M, Robertson ES. Tumor viruses and cancer biology: Modulating signaling pathways for therapeutic intervention. Cancer Biol Ther. 2010 Nov 15;10(10):961-78. doi: 10.4161/cbt.10.10.13923. Epub 2010 Nov 15. — View Citation
Si Y, Deng Z, Lan G, Du H, Wang Y, Si J, Wei J, Weng J, Qin Y, Huang B, Yang Y, Qin Y. The Safety and Immunological Effects of rAd5-EBV-LMP2 Vaccine in Nasopharyngeal Carcinoma Patients: A Phase I Clinical Trial and Two-Year Follow-Up. Chem Pharm Bull (Tokyo). 2016;64(8):1118-23. doi: 10.1248/cpb.c16-00114. — View Citation
Taylor GS, Jia H, Harrington K, Lee LW, Turner J, Ladell K, Price DA, Tanday M, Matthews J, Roberts C, Edwards C, McGuigan L, Hartley A, Wilson S, Hui EP, Chan AT, Rickinson AB, Steven NM. A recombinant modified vaccinia ankara vaccine encoding Epstein-Barr Virus (EBV) target antigens: a phase I trial in UK patients with EBV-positive cancer. Clin Cancer Res. 2014 Oct 1;20(19):5009-22. doi: 10.1158/1078-0432.CCR-14-1122-T. Epub 2014 Aug 14. — View Citation
Tsao SW, Tsang CM, To KF, Lo KW. The role of Epstein-Barr virus in epithelial malignancies. J Pathol. 2015 Jan;235(2):323-33. doi: 10.1002/path.4448. — View Citation
Wang F, Qin Z, Lu H, He S, Luo J, Jin C, Song X. Clinical translation of gene medicine. J Gene Med. 2019 Jul;21(7):e3108. doi: 10.1002/jgm.3108. Epub 2019 Jul 15. — View Citation
Young LS, Yap LF, Murray PG. Epstein-Barr virus: more than 50 years old and still providing surprises. Nat Rev Cancer. 2016 Dec;16(12):789-802. doi: 10.1038/nrc.2016.92. Epub 2016 Sep 30. — View Citation
* Note: There are 18 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Adverse events | Adverse events defined as the number of participants with adverse events according | up to 12 months | |
Primary | Objective response rate | ORR is defined as the percentage of patients who achieve a response, which can either be complete response (complete disappearance of lesions) or partial response (reduction in the sum of maximal tumor diameters by at least 30% or more) | up to 12 months | |
Primary | Progress-Free Survival | PFS is defined as the time from the administration of the first dose to first disease | up to 12 months | |
Primary | Overall Survival | OS is defined as the time from the administration of the first dose to death. | up to 12 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02041871 -
Interest of PReOPerative Immunonutrition in Liver Surgery for Cancer
|
N/A | |
Completed |
NCT03110783 -
Bioseal Dural Sealing Study BIOS-14-001
|
Phase 3 | |
Recruiting |
NCT05516914 -
A Phase Ib/II Clinical Trial of LBL-007 Combined With Tislelizumab in the Treatment of Malignant Tumors
|
Phase 1/Phase 2 | |
Completed |
NCT02534506 -
Study of Urelumab in Subjects With Advanced and/or Metastatic Malignant Tumors
|
Phase 1 | |
Recruiting |
NCT05987098 -
BBPA PET/CT in Patients With Malignant Tumors
|
N/A | |
Not yet recruiting |
NCT01092247 -
The Effect of Ketogenic Diet on Malignant Tumors- Recurrence and Progress
|
N/A | |
Recruiting |
NCT03160599 -
Restricted Calorie Ketogenic Diet as a Treatment in Malignant Tumors
|
N/A | |
Recruiting |
NCT04702841 -
CAR - γ δ T Cells in the Treatment of Relapsed and Refractory CD7 Positive T Cell-derived Malignant Tumors
|
Early Phase 1 | |
Completed |
NCT00165100 -
Dynamic Area Telethermometry (DAT) as an Imaging Modality in Patients With Cancer
|
N/A | |
Suspended |
NCT05615974 -
A Phase I/II Study of LM-101 Injection in Patients With Advanced Malignant Tumors
|
Phase 1/Phase 2 | |
Completed |
NCT03542773 -
Targeted Imaging of Glutamate Carboxypeptidase II With DCFPyL-PET
|
Phase 1 | |
Completed |
NCT05293990 -
Usefulness of Gadovist-enhanced FLAIR Imaging
|
N/A | |
Completed |
NCT01509612 -
Additive Homeopathy in Cancer Patients
|
Phase 3 | |
Completed |
NCT01678690 -
An Exploratory Study of Gemcitabine Hydrochloride Oral Formulation (D07001-F4) in Subjects With Malignant Tumors
|
Phase 0 | |
Suspended |
NCT06270394 -
FAP PET/CT or PET/MR Production in the Diagnosis, Staging, and Efficacy Assessment of Malignant Tumors Application
|
N/A | |
Completed |
NCT00412503 -
Temozolomide in Association With Topotecan in Refractory or Relapsed Malignant Tumors in Children and Adolescents
|
Phase 1 |