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

NCT06991738 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001532001532-DK
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Thyroid Cancer

Keywords

Thyroid Cancer; H(SqrRoot) rthle cell thyroid cancer; 177Lu-DOTA-EB-TATE

Outcome Measures

Primary Outcomes (3)

• 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 identify the dose-limiting toxicities (DLTs) of escalating doses of 177Lu DOTA EB TATE based on individualized dosimetry.

  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 Outcomes (6)

• 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

Study Arms (3)

177Lu-DOTA-EB-TATE

EXPERIMENTAL

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

Drug: 177Lu-DOTA-EB-TATE

68Ga-DOTA-TATE PET Scan

OTHER

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.

Diagnostic Test: 68Ga-DOTA-TATE PET Scan

Amino acid infusions

OTHER

Concomitant administration of an amino acid infusion with the study drug 177Lu-DOTA-EB-TATE is for renal protection.

Other: Amino acid infusions; Drug: 177Lu-DOTA-EB-TATE

Interventions

Amino acid infusions OTHER

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.

Amino acid infusions

68Ga-DOTA-TATE PET Scan DIAGNOSTIC_TEST

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.

68Ga-DOTA-TATE PET Scan

177Lu-DOTA-EB-TATE DRUG

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.

177Lu-DOTA-EB-TATE; Amino acid infusions

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Aged 18 years or older.
• Metastatic RAI-non-responsive and/or RAI-non-avid oncocytic (Hurthle cell) thyroid cancer.
• Progressive disease by RECIST 1.1 criteria, with or without symptoms within the last 12 months. This applies to patients with non-measurable disease by RECIST 1.1 criteria, who will be eligible if they have evidence of progression as defined by the development of new lesions within the last 12 months.
• High expression of SSTR2 in at least one metastatic lesion as documented by 68Ga-DOTATATE PET/CT with SUVmax \> SUVmax of the liver consistent with Krenning score of \>2 or SUVmax \>= 13 based on scan performed within 12 weeks of anticipated enrollment.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnant or breastfeeding.
• NET/PET score of 5 by imaging with 68Ga-DOTATATE PET/CT and 18FDG-PET/CT and defined more than 2 lesions that are SSTR2 negative but 18FDG positive and/or more than 2 lesions that have significantly higher uptake of 18FDG than 68Ga-DOTATATE
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-DOTA-EB-TATE as assessed from medical record.
• Patient weight \> 500 lbs. (due to the PET scanner table limit).
• Inability to tolerate at least one modality of diagnostic anatomic imaging, such as CT or MRI.
• Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 4 weeks or 4 half-lives (whichever is longer), before the first administration of study drug.
• Previous surgery \< 6 weeks prior to the start of participation in this study, or participant has not fully recovered from major surgery, or has suffered significant traumatic injury prior the first dose of study drug or expects to have major surgery during the study period or within 3 months after the last dose of study drug.
• Life expectancy \< 6 months as assessed by the treating physician.
• Karnofsky performance status scale \< 70%.
• Inability or unwillingness to use adequate contraception prior to study entry and for the duration of study participation, including follow-up (7 months after the last dose of study drug for women and 4 months for men). The adequate contraception consists of intrauterine device, contraceptive implant, hormonal contraception or a double-barrier method. If the patient is status post tubal ligation, status post hysterectomy and/or oophorectomy, or their male partners are status post vasectomy, no additional method of contraception is required.
• Deteriorated renal function, as indicated by a creatinine clearance \<60 mL/min calculated by the Cockcroft-Gault Equation. The calculated creatinine clearance can be confirmed by measured creatinine clearance.
• Having only one functional kidney, due to potential nephrotoxicity.
• Patients who have had any prior EBRT dose to either kidney.
• Deteriorated bone marrow function, as indicated by:

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

(177)Lu-DOTA-EB-TATE

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Joanna Klubo-Gwiezdzinska, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Padmasree Veeraraghavan, R.N.

CONTACT

(301) 451-7710; padmasree.veeraraghavan@nih.gov

Joanna Klubo-Gwiezdzinska, M.D.

CONTACT

(301) 496-5052; joanna.klubo-gwiezdzinska@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2025
• First Posted: May 28, 2025
• Study Start (Estimated): May 11, 2026
• Primary Completion (Estimated): July 1, 2032
• Study Completion (Estimated): August 1, 2032
• Last Updated: May 6, 2026

Record last verified: 2026-02-17

Locations

US (1)