177Lu-DOTA-EB-TATE in Adult Patients With Metastatic, Radioactive Iodine Non-Responsive Oncocytic (Hurthle-Cell) Thyroid Cancer

Description

Study Description:

The proposed indication is for the treatment of somatostatin receptor-positive radioactive iodine (RAI) non-responsive metastatic oncocytic (Hurthle 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.
* Analyse early efficacy of 177Lu-DOTA-EB-TATE in 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).

Objectives:

Primary Objectives:

* 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 identify the dose-limiting toxicities (DLTs) of escalating doses of 177Lu-DOTA-EB-TATE based on individualized dosimetry.
* 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
* To assess the objective response rate (ORR) and disease control rate (DCR) and association between the specific absorbed dose per lesion of 177Lu-DOTA-EB-TATE.
* To assess the association between the specific absorbed dose per lesion with the tumor response as defined by RECIST 1.1 criteria.
* To assess changes in circulating levels of the tumor marker thyroglobulin (Tg) and anti-Tg antibodies throughout study participation.
* To assess the quality of life (QoL) throughout administration of 177Lu-DOTA-EB-TATE cycles.
* To capture extended safety data by assessing the rate of late adverse events (AEs) and serious adverse events (SAEs).

Endpoints:

Primary Endpoints:

* The primary safety endpoint is a combination of serious adverse events (SAEs), and dose limiting toxicities (DLTs) using CTCAE v5.0. We will also assess the number of participants with treat-related adverse events.
* The primary efficacy endpoint is progression free survival (PFS) at 6 months after the last cycle, where progression is defined by RECIST 1.1 criteria.
* For determination of the optimal dose, each patient will be classified into one of four categories according to the presence or absence of toxicity and efficacy at 8-12 weeks after each cycle and at 6 months after the last cycle.

Secondary Endpoints:

* Radiation-absorbed doses following each cycle of study intervention, normalized to administered activity, including:
* Residence time of 177Lu-DOTA-EB-TATE in liver, spleen, kidneys, whole body and blood pool.
* Specific absorbed dose per organ (Gy/GBq) (using MIRD method as implemented in OLINDA/EXM).
* Cumulative absorbed organ doses (Gy).
* Bone Marrow dose using blood-based method.
* Standardized uptake value (SUV) normalized to lean body mass for maximum (SULmax) in discernible target lesions.
* SULmax in liver, spleen, kidneys, bone marrow and pituitary if visible.
* Tumor response documented as objective response rate (ORR) and disease control rate (DCR) assessed at 24 (+/-2 weeks) and 52 (+/-2 weeks), as well as 2, 3, 4, and 5 years (+/-3 months) after completion of all treatment cycles, as defined by RECIST 1.1 criteria.
* Association between ORR/DCR and tumor absorbed dose using Spearman rank correlation 24 (+/-2 weeks) and 52 (+/-2 weeks), as well as 2, 3, 4, and 5 years (+/-3 months) after last dose of study drug
* Change in thyroglobulin (Tg) and anti-Tg antibodies from baseline to 24 (+/-2 weeks) and 52 (+/-2 weeks) post last dose of the study drug.
* ThyPRO QoL scores at baseline, after each study drug cycle, and at 24 (+/-2 weeks) and 52 (+/-2 weeks) post last dose of the study drug.
* AEs and SAEs at 2, 3, 4, 5 years (+/-3 months) of follow up after last dose of study drug.