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

• 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
• 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

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).

我们计划对患有转移性放射性碘无反应性心率的成年患者进行 177Lu-DOTA-EB-TATE 剂量递增的 3 剂量方案的安全性、剂量测定和疗效进行 1/2 期开放标签研究-细胞甲状腺癌 拟议的适应症是用于治疗成人生长抑素受体阳性放射性碘（RAI）无反应性转移性甲状腺激素（HTC）癌。 我们假设这项研究将解决以下问题： 评估 177Lu-DOTA-EB-TATE 是否安全且可耐受。 分析 177Lu-DOTA-EB-TATE 治疗转移性 HTC 的早期疗效。 确定 177Lu-DOTA-EB-TATE 的最佳剂量，其特点是基于贝叶斯最佳间隔 I/II 期事件时间 (TITE-BOIN12)，在功效和毒性之间进行最佳权衡 主要目标： 1/2 阶段 基于TITE-BOIN12 1/2期临床试验设计，确定治疗转移性HTC既安全又具有足够疗效的177Lu-DOTA-EB-TATE最佳剂量 根据发生治疗相关不良事件的患者数量来评估 177Lu DOTA EB TATE 的安全性。 旨在确定 177Lu DOTA EB TATE 在最多 3 个周期（间隔 82 周）中，肾脏累积暴露量不超过 27 Gy 且骨髓累积暴露量不超过 2 Gy 的剂量逐渐增加的剂量限制毒性 (DLT)。 旨在评估 177Lu DOTA EB TATE 对改善转移性 RAI 无反应 HTC 参与者在最后一个研究药物周期后 6 个月的无进展生存期 (PFS) 的疗效。 次要目标： 确定 177Lu-DOTA-EB-TATE 每个周期后患者的剂量测定，包括以下内容： o 177Lu-DOTA-EB-TATE 的停留时间，包括肝脏、脾脏、肾脏、全身和血池。 o 每个器官的特定吸收剂量 (Gy/GBq)（使用 OLINDA/EXM 中实施的 MIRD 方法） o 器官累积吸收剂量 (Gy) o 使用基于血液的方法进行骨髓剂量。 o 标准化摄取值 (SUV)，归一化为可辨别目标病变中的最大去脂体重 (SULmax) o 肝脏、脾脏、肾脏、骨髓和垂体中的 SULmax（如果可见）。 评估根据 RECIST 1.1 标准定义的治疗后 6 个月和 12 个月的 177Lu DOTA EB TATE 治疗后的客观缓解率 (ORR)。根据 RECIST 1.1 定义，具有目标病变和非目标病变的患者将纳入分析。 评估每个病灶的具体吸收剂量与根据 RECIST 1.1 标准定义的肿瘤反应之间的关联，在研究药物最后一次给药后 6 个月和 12 个月的随访中具有里程碑意义。 为了评估肿瘤标志物甲状腺球蛋白 (Tg) 和抗 Tg 抗体从治疗前到最后一次服用研究药物后 6 个月和 12 个月的变化。 使用 ThyPRO 问卷评估基线、每个治疗周期后以及治疗完成后 6 个月和 12 个月的生活质量 (QoL)，该问卷已针对甲状腺疾病患者进行了验证。 将招募最多 18 名 18 岁或以上患有转移性 RAI 无反应或 RAI 非强烈 Hrthle 细胞甲状腺癌的男性和女性成年人，以便有 15 名可评估患者（每组 3 名患者，最多 5 个组） 。