Somatostatin receptors in the diagnosis and treatment of thyroid cancer

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

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 8 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).