Somatostatin receptors in the diagnosis and treatment of thyroid cancer

生长抑素受体在甲状腺癌诊断和治疗中的作用

基本信息

批准号：
10700681
负责人：
Joanna Klubo-Gwiezdzinska
金额：
$ 24.8万
依托单位：
NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10700681
关键词：
Address Adult Adverse event Aftercare Blood Bone Marrow Case Series Cells Diagnosis Diagnostic Imaging Dose Dose-Limiting Enrollment Evaluable Disease Event Exposure to Female Kidney Lesion Liver Malignant - descriptor Malignant neoplasm of thyroid Methods Neuroendocrine Tumors Organ Participant Patients Pharmaceutical Preparations Phase Phase I/II Clinical Trial Pituitary Gland Progression-Free Survivals Quality of life Questionnaires Radioactive Iodine Radiolabeled Refractory Regimen SSTR2 gene Safety Somatostatin Receptor Spleen Standardization Therapeutic Thyroglobulin Thyroglobulin antibody Thyroid Diseases Thyroid Gland Thyroid Nodule Thyroidectomy Time Toxic effect Treatment Efficacy Tumor Markers United States National Institutes of Health analog base cohort dosimetry follow-up improved lean body mass male molecular targeted therapies objective response rate open label phase 1 designs radioiodine therapy residence response safety study somatostatin receptor 2 tumor uptake

Address Adult Adverse event Aftercare Blood Bone Marrow Case Series Cells Diagnosis Diagnostic Imaging Dose Dose-Limiting Enrollment Evaluable Disease Event Exposure to Female Kidney Lesion Liver Malignant - descriptor Malignant neoplasm of thyroid Methods Neuroendocrine Tumors Organ Participant Patients Pharmaceutical Preparations Phase Phase I/II Clinical Trial Pituitary Gland Progression-Free Survivals Quality of life Questionnaires Radioactive Iodine Radiolabeled Refractory Regimen SSTR2 gene Safety Somatostatin Receptor Spleen Standardization Therapeutic Thyroglobulin Thyroglobulin antibody Thyroid Diseases Thyroid Gland Thyroid Nodule Thyroidectomy Time Toxic effect Treatment Efficacy Tumor Markers United States National Institutes of Health analog base cohort dosimetry follow-up improved lean body mass male molecular targeted therapies objective response rate open label phase 1 designs radioiodine therapy residence response safety study somatostatin receptor 2 tumor uptake

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项目摘要

We plan to conduct a Phase 1/2, Open-Label Study of the Safety, Dosimetry and Efficacy of a 3-Dose Regimen of Escalating Doses of 177Lu-DOTA-EB-TATE in Adult Patients with Metastatic, Radioactive Iodine Non-Responsive Hrthle-Cell Thyroid Cancer The proposed indication is for the treatment of somatostatin receptor-positive radioactive iodine (RAI) non-responsive metastatic Hrthle cell thyroid (HTC) cancer in adults. We hypothesize that this study will address the following: Evaluate if 177Lu-DOTA-EB-TATE is safe and tolerable. Analyze early efficacy of 177Lu-DOTA-EB-TATE in therapy of metastatic HTC. Establish the optimal dose of 177Lu-DOTA-EB-TATE that is characterized by an optimal trade-off between efficacy and toxicity based on Bayesian optimal interval phase I/II time-to-event (TITE-BOIN12) Primary Objectives: Phase 1/2 To determine the optimal dose of 177Lu-DOTA-EB-TATE that is both safe and shows sufficient efficacy for treatment of metastatic HTC based on TITE-BOIN12 design of phase 1/2 clinical trial To evaluate the safety of 177Lu DOTA EB TATE assessed from the number of patients with treatment-related adverse events. To identify the dose-limiting toxicities (DLTs) of escalating doses of 177Lu DOTA EB TATE up to 27 Gy cumulative exposure to the kidneys and not exceeding 2 Gy cumulative exposure to the bone marrow in up to 3 cycles 82 weeks apart. To assess the efficacy of 177Lu DOTA EB TATE to improve upon progression-free survival (PFS) at 6 months after the last cycle of the study drug in participants with metastatic RAI-non-responsive HTC. Secondary Objectives: To determine dosimetry in patients following each cycle of 177Lu-DOTA-EB-TATE, including the following: o Residence time of 177Lu-DOTA-EB-TATE including liver, spleen, kidneys, whole body and blood pool. o Specific absorbed dose per organ (Gy/GBq) (using MIRD method as implemented in OLINDA/EXM) o Cumulative absorbed organ doses (Gy) o Bone Marrow dose using blood-based method. o Standardized uptake value (SUV) normalized to lean body mass for maximum (SULmax) in discernible target lesions o SULmax in liver, spleen, kidneys, bone marrow and pituitary if visible. To assess the objective response rate (ORR) after the therapy with 177Lu DOTA EB TATE at 6- and 12-months post-treatment defined by RECIST 1.1 criteria. Patients with target and non-target lesions per RECIST 1.1 definitions will be included in the analysis. To assess the association between the specific absorbed dose per lesion with the tumor response as defined by RECIST 1.1 criteria at 6 and 12 months follow up landmark post last dose of the study drug. To assess the tumor marker thyroglobulin (Tg) and anti-Tg antibodies change from pre-treatment to 6- and 12-months post last dose of the study drug. To assess the quality of life (QoL) at baseline and after each treatment cycle as well as at 6- and 12-months landmarks post completion of the therapy, using ThyPRO questionnaire, validated for patients with thyroid disorders. Up to 18 male and female adults, 18 years or older, with metastatic RAI-non-responsive or RAI non-avid Hrthle cell thyroid cancer will be enrolled in order to have 15 evaluable patients (3 patients per cohort, up to 5 cohorts).

我们计划对成人转移性，放射性碘非反应性HRTHLE-HRTHLE-Cell-Cell-Cell-Cell-Cell-Cell-Cell-Cell-Cell-Cell-Cell-Cell-Cell-Cell-Cell-Cell-Cell-hrthle-Cell-Cell-Cell-Cell-Cell-Cell-Cell-hrthle-hrthle-Cell-Cell-Cell-Cell-Cell-Cell thy-Cell-Cell-Cell-Cell thy-Cell-Cell-Cell甲状腺甲状腺癌甲状腺癌甲状腺癌甲状腺癌甲状腺癌甲状腺癌升高，对3剂剂量的安全性，剂量和疗效进行1/2阶段的开放性研究研究。所提出的指示是用于治疗成人生长抑素受体阳性放射性碘（RAI）非反应性转移性HRTHLE细胞甲状腺（HTC）癌症。我们假设这项研究将解决以下内容：评估177lu-dota-eb-tate是否安全可容忍。分析177LU-DOTA-EB-TATE在转移性HTC治疗中的早期疗效。建立177LU-DOTA-EB-TATE的最佳剂量，其特征是基于贝叶斯最佳间隔I/II/II/II的最佳毒性和毒性之间的最佳权衡取舍（Tite-boin12）主要目标：阶段1/2 确定既安全又安全的177lu-dota-eb-tate的最佳剂量为了评估根据患有治疗相关不良事件的患者数量评估的177lu dota eb tate的安全性。为了确定177lu dota eb tate的剂量限制毒性（DLT），最多27 Gy累积暴露于肾脏，并且不超过2 Gy累积的累积暴露于骨髓中，最多3个循环分隔了82周。为了评估研究药物最后一个周期后6个月，在转移性rai-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-non-not-eb tate疗效中提高无进展生存率（PFS）。次要目标：确定每个周期177lu-dota-eb-tate之后患者的剂量测定法，包括以下内容： o 177lu-dota-eb-tate的停留时间，包括肝脏，脾脏，肾脏，全身和血液库。 o特定的每个器官吸收剂量（GY/GBQ）（使用Olinda/exm中实现的MIRD方法） o累积吸收器官剂量（GY） o使用基于血液的方法骨髓剂量。 o标准化摄取值（SUV）在可识别的目标病变中归一化至瘦体重（SULMAX） o肝，脾，肾脏，骨髓和垂体（如果可见）。在治疗后用Recist 1.1标准定义的6个月和12个月的治疗后，用177lu dota eb tate进行治疗后的客观反应率（ORR）。分析将包括靶标和非目标病变1.1定义的患者。为了评估每个病变的特异性吸收剂量与肿瘤反应的肿瘤反应，如6和12个月时的recist 1.1标准所定义的，在研究药物的最后剂量后跟进地标。为了评估研究药物的最后剂量后，肿瘤标记物（TG）和抗TG抗体在最后剂量后的6个月和12个月的变化变化。在完成治疗后完成治疗后的6个月和12个月地标在基线和每个治疗周期之后的生活质量（QOL），使用Thypro问卷，该问卷对甲状腺疾病的患者进行了验证。将招募多达18岁的18岁或女性成年人，年龄在18岁或以上，具有转移性RAI反应性或RAI非AVID HRTHLE细胞甲状腺癌，以便患有15名可评估患者（每名队列3例，最多5个同类群）。