Background: Oncocytic (Hurthle cell) thyroid cancer (HTC) is a rare disease with few treatment options. Researchers are developing a radioactive drug that targets a protein that appears in high numbers on HTC cancer cells. Objective: To test a radioactive drug (177LuDOTA-EB-TATE) in people with HTC. Eligibility: People aged 18 years and older with HTC. The HTC must have failed to respond to conventional radioactive treatment; it must also have spread to other parts of the body. Design: Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and a test of their heart function. 177LuDOTA-EB-TATE is infused into a vein. Participants will receive 4 infusions spaced 8 to 12 weeks apart. They will stay in the hospital for 4 to 10 days after each infusion. During and after each infusion, participants will remain in a lead-lined room until their radiation levels go down; this usually takes about 24 hours. Participants will have 4 to 6 follow-up visits in the weeks after each infusion. Procedures will vary at each visit, but may include more imaging scans; blood and urine tests; and tests of heart function. Participants will have 2 single-photon emission computerized tomography (SPECT) scans. SPECT scans show where the study drug is sticking to tumors or maybe other parts of their body. They will lie on a table while a machine rotates around them. Participants will fill in questionnaires about how their thyroid condition affects their life. Participants will have follow-ups visits for 5 years after their last study treatment.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
68Ga-DOTATATE is administered via intravenous injection of 5 1 mCi in a volume of 3 - 5 ml containing up to 50 micrograms \[68Ga\] DOTATATE.
Appropriate amino acid solutions infused for this purpose should have a total lysine and arginine content between 18g and 25g and have an osmolality of \<= 1050 mOsmol. Concomitant administration of an amino acid infusion with the study drug 177Lu-DOTA-EB-TATE is for renal protection.
Each single-dose vial contains sodium acetate (24.6 mg/mL), gentisic acid (3.7 mg/mL), L-ascorbate (0.445 mg/mL), DTPA (0.051 mg/mL). 177Lu-DOTA-EB-TATE, is a long-acting radiopharmaceutical for PRRT. It consists of a somatostatin analog peptide (TATE) conjugated with a truncated Evans blue (EB) molecule and the metal chelator 1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid (DOTA) with the radioisotope 177Lu stably complexed.
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
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 [1, 2].
Time frame: 8-12 weeks
To identify the dose-limiting toxicities (DLTs) of escalating doses of 177Lu DOTA EB TATE based on individualized dosimetry.
Time frame: 8-12 weeks
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.
Time frame: 8-12 weeks
To determine dosimetry in patients following each cycle of 177Lu-DOTA-EB-TATE
Time frame: 8-12 weeks
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.
Time frame: 24 (+/-2 weeks) and 52 (+/-2 weeks), as well as 2, 3, 4, and 5 years (+/-3 months) after last dose of study drug
To assess the association between the specific absorbed dose per lesion with the tumor response as defined by RECIST 1.1 criteria.
Time frame: 24 (+/-2 weeks) and 52 (+/-2 weeks), as well as 2, 3, 4, and 5 years (+/-3 months) after completion of all treatment cycles
To assess changes in circulating levels of the tumor marker thyroglobulin (Tg) and anti-Tg antibodies throughout study participation.
Time frame: baseline to 24 (+/-2 weeks) and 52 (+/-2 weeks) post last dose of the study drug
To assess the quality of life (QoL) throughout administration of 177Lu DOTA EB TATE cycles.
Time frame: at baseline, after each study drug cycle, and at 24 (+/-2 weeks) and 52 (+/-2 weeks) post last dose of the study drug
To capture extended safety data by assessing the rate of late adverse events (AEs) and serious adverse events (SAEs).
Time frame: 2, 3, 4, 5 years (+/-3 months) of follow up after last dose of study drug.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.