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Treatment of advanced endocrine tumors, including adrenal corticocarcnioma (ACC), medullary thyroid carcinoma (MTC), thymic neuroendocrine tumor and pancreatic neuroendocrine tumor is challenging. Previous genomic profiling studies showed they presented a number of somatic mutations. The tumors Individualized mRNA neoantigen vaccine provide a promising solution since a significant portion of these tumors showed high quality of tumor specific neoantigen. The primary objective is to observe and evaluate the safety and tolerability of individualized mRNA neoantigen vaccine (mRNA-0523-L001) for the treatment of advanced endocrine tumors, failure of standard treatment or no standard treatment currently available. The secondary objective is to observe the preliminary efficacy of mRNA-0523-L001 for the treatment of advanced endocrine tumors, failure of standard treatment or no standard treatment currently available, including:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| mRNA-0523-L001 | Experimental | individualized mRNA neoantigen vaccine (mRNA-0523-L001) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| individualized mRNA neoantigen vaccine (mRNA-0523-L001) | Biological | Individualized mRNA neoantigen vaccine (mRNA-0523-L001) will be injected intramuscularly every 21 days for 9 cycles. Dose escalation will be administered in 3 patients. 18 additional patients will be recruited and administered at the maximum tolerated(MTD) dose for all nine cycles. Injection of mRNA-0523-L001 will continue if an objective response is observed until the discontinuation criteria are met. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum tolerated dose (MTD) or Dose-limiting toxicity (DLT).If MTD is not reached, Biologically Effective Dose (BED)tumor neoantigen. | The highest dose of a drug or treatment that does not cause unacceptable side effects. | At the end of cycle 1(each cycle is 21 days) |
| Incidence of treatment-related adverse events. | According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). | At the end of cycle 1(each cycle is 21 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Reaction of antigen-specific T cells in peripheral blood. | mRNA-0523-L001 personalized tumor vaccine induces neoantigen specific CD4+and CD8+T lymphocyte responses. | At the end of cycle 1(each cycle is 21 days) |
| Objective tumor response rate (ORR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lei Ye | Contact | 15201909962 | lei_yelei@163.com | |
| Luming Wu | Contact | 13818707008 | wulum@126.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ruijin hospital, Shanghai Jiao-Tong University School of Medicine | Recruiting | Shanghai | Shanghai Municipality | 200025 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
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| 35895692 | Background | Saltiki K, Simeakis G, Karapanou O, Alevizaki M. MANAGEMENT OF ENDOCRINE DISEASE: Medullary thyroid cancer: from molecular biology and therapeutic pitfalls to future targeted treatment perspectives. Eur J Endocrinol. 2022 Jul 26;187(3):R53-R63. doi: 10.1530/EJE-22-0312. Print 2022 Sep 1. |
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ORR calculates the ratio of the number of patients whose best response is complete remission (CR) or partial remission (PR) to the total number of evaluable patients according to RECIST 1.1 criteria. Those who have not been evaluated for lesion and tumor response will be regarded as non-evaluable patients and will not be counted.
| At the end of cycle 1(each cycle is 21 days) |
| Disease control rate (DCR) | DCR calculates the ratio of the number of patients whose best response is complete remission (CR), or partial remission (PR), or stable disease (SD) to the total number of evaluable patients according to RECIST 1.1 criteria. Those who have not been evaluated for lesion and tumor response will be regarded as non-evaluable patients and will not be counted. | At the end of cycle 1(each cycle is 21 days) |
| Progressive free survival (PFS) | Progression-free Survival of Personalized mRNA Tumor Vaccine. | At the end of cycle 1(each cycle is 21 days) |
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| ID | Term |
|---|---|
| D018268 | Adrenocortical Carcinoma |
| D018276 | Carcinoma, Medullary |
| D007516 | Adenoma, Islet Cell |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D000306 | Adrenal Cortex Neoplasms |
| D000310 | Adrenal Gland Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D000303 | Adrenal Cortex Diseases |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
| D018278 | Carcinoma, Neuroendocrine |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D018299 | Neoplasms, Ductal, Lobular, and Medullary |
| D009380 | Neoplasms, Nerve Tissue |
| D000236 | Adenoma |
| D010190 | Pancreatic Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
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