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Targeted alpha-emitter therapy of patients with PRRT refractory neuroendocrine tumors

PRRT难治性神经内分泌肿瘤患者的靶向α发射体治疗

基本信息

批准号：
10483180
负责人：
Izabela Tworowska
金额：
$ 145.18万
依托单位：
RADIOMEDIX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-07 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10483180
关键词：
Address Affect Agonist Biological Markers Clinical Clinical Protocols Clinical Research Contracts Control Groups Development Diagnosis Disease Dose Drug Targeting Enrollment Funding Grant Heterogeneity High-LET Radiation In complete remission Institutional Review Boards Investigational Drugs Investments Label Length Location Measures Multi-site clinical study Neoplasms Neuroblastoma Neuroendocrine Cell Neuroendocrine Therapy Neuroendocrine Tumors Neurosecretory Systems Normal tissue morphology Octreotide Operative Surgical Procedures Organ PET/CT scan Patient-Focused Outcomes Patients Peptide Receptor Pharmaceutical Preparations Phase Primary Neoplasm Production Progression-Free Survivals Property Protocols documentation Radiology Specialty Radionuclide therapy Refractory Research Resistance Safety Small Business Innovation Research Grant Somatostatin Somatostatin Receptor Symptoms Targeted Radiotherapy Testing Time X-Ray Computed Tomography cancer cell chemotherapy clinical efficacy clinical practice cohort commercialization dosimetry ds-DNA effective therapy efficacy evaluation efficacy outcomes improved innovation interest liquid biopsy manufacturing facility meetings next generation objective response rate open label overexpression partial response phase 1 study phase 2 study physical property response side effect somatostatin analog somatostatin receptor 2 therapy development treatment choice tumor tumor progression

项目摘要

PROJECT SUMMARY A peptide receptor radionuclide therapy (PRRT) using beta-emitter-labeled somatostatin analogs has showed increase in the progression-free-survival (PFS) of 177Lu-dotatate treated subjects, however the objective response rate of this group is rather low only 18% compare to control group. In addition, the number of complete responses and partial responses seen in the daily clinical practice in Lutathera treated patients is also low. This is due to the heterogeneity of neuroendocrine tumors; advanced stage of disease at the time of diagnosis; and more importantly tumor resistance to beta-emitter PRRT developed during the therapy. The targeted alpha- emitter therapy (TAT) of neuroendocrine tumors can overcome these limitations and our Phase I dose escalation studies of 212Pb-DOTAMTATE (AlphaMedix) provide clinical evidence supporting this statement. Our dose Phase I study determined SAFE and HIGHLY EFFECTIVE DOSE of AlphaMedixTM in PRRT naïve patients with metastatic neuroendocrine tumors regardless of the location of the primary tumor. All patients treated with this effective dose have shown the Objective Radiologic Response (ORR 83%) by RECIST criteria and almost complete response by NETSPOT PET/CT imaging. The main objective of proposed study is determination of the safety, PK, and efficacy of Alphamedix in PRRT refractory patients who failed and progressed after Lutathera. This will be accomplished during Phase I clinical study (amended IND 135150), followed by Phase II study (Protocol Number: RMX-Alpha-R020). OBJECTIVE 1. Phase I safety, efficacy and PK studies of the effective dose of Alphamedix in PRRT-refractory patients regardless the primary origin the tumor. With successful completion of this objective, we will confirm the efficacy and safety of recommended doses of Alphamedix, compile all modules for Phase II clinical studies and request type B meeting and submit Phase II clinical protocol to IRB and FDA. OBJECTIVE 2. Phase II non-randomized, open-label, multi-center clinical studies of AlphaMedix in PRRT refractory patients. With successful completion of the objective, we will determine the median Progression free survival (mPFS) and the Overall Survival (OS) of NETs patients, as well as their Time to Tumor Progression (TTP), and safety of the recommended doses of AlphaMedix.

项目总结