177Lu-DOTA-EB-TATE in Adult Patients With Metastatic, Radioactive Iodine Non-Responsive Oncocytic (Hurthle-Cell) Thyroid Cancer
- Conditions
- Thyroid Cancer
- Interventions
- Registration Number
- NCT06991738
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 18
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 177Lu-DOTA-EB-TATE 177Lu-DOTA-EB-TATE 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 Oncocytic (Hurthle-Cell) Thyroid Cancer 68Ga-DOTA-TATE PET Scan 68Ga-DOTA-TATE PET Scan The radiopharmaceutical 68Ga-DOTATATE is acquired by the NIH PET department in the Clinical Center. The radiopharmaceutical is synthetized on the day of the study and a premade dose of 5 mCi is administered. Amino acid infusions 177Lu-DOTA-EB-TATE Concomitant administration of an amino acid infusion with the study drug 177Lu-DOTA-EB-TATE is for renal protection. Amino acid infusions Amino acid infusions Concomitant administration of an amino acid infusion with the study drug 177Lu-DOTA-EB-TATE is for renal protection.
- Primary Outcome Measures
Name Time Method To identify the dose-limiting toxicities (DLTs) of escalating doses of 177Lu DOTA EB TATE based on individualized dosimetry. 8-12 weeks 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]. 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. 8-12 weeks
- Secondary Outcome Measures
Name Time Method To determine dosimetry in patients following each cycle of 177Lu-DOTA-EB-TATE 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. 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. 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. 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. 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). 2, 3, 4, 5 years (+/-3 months) of follow up after last dose of study drug.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
National Institutes of Health Clinical Center🇺🇸Bethesda, Maryland, United StatesNIH Clinical Center Office of Patient Recruitment (OPR)Contact800-411-1222ccopr@nih.gov