177Lu-CTR-FAPI for thyroid cancer

177Lu-CTR-FAPI for the Treatment of Thyroid Cancer: A Prospective, Multi-center, Open-labeled, Single-arm, Phase I Study

This will try a radioactive drug called 177Lu-CTR-FAPI in people with progressive, radioactive iodine–refractory thyroid cancer to see if it is safe and helps shrink tumors.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 2 sites (Beijing and 1 other locations)
• Trial ID: NCT07438847 on ClinicalTrials.gov

What this trial studies

This is a multi-center, open-label, single-arm phase I trial using a 3+3 dose-escalation design to characterize safety and dose-limiting toxicities of 177Lu-CTR-FAPI. Up to 12 eligible participants will receive intravenous 177Lu-CTR-FAPI starting at 100 mCi with 50 mCi dose increments, given every 6 weeks for up to four cycles while monitoring adverse events and dosimetry. Primary endpoint is safety and determination of the maximum tolerated dose; secondary endpoints include biochemical and radiological response and quality-of-life measures. Eligibility requires progressive, measurable thyroid cancer with high CTR-FAPI uptake on 68Ga-CTR-FAPI PET/CT and adequate performance status.

Who should consider this trial

Good fit: Ideal candidates are adults with progressive, measurable thyroid cancer that is radioactive iodine–refractory, who have CTR-FAPI–positive lesions on 68Ga-CTR-FAPI PET/CT (SUVmax > 10 in most lesions), ECOG ≤ 2, and life expectancy > 6 months.

Not a fit: Patients whose tumors show low or absent CTR-FAPI uptake, who have poor performance status, very limited life expectancy, or resectable localized disease are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, this approach could provide a new targeted radionuclide therapy option for patients with radioactive iodine–refractory thyroid cancer that may improve tumor control and symptoms.

How similar studies have performed: Early clinical reports of FAPI-targeted radioligand therapies have shown promising tumor uptake and preliminary responses in several cancer types, but thyroid-specific evidence is limited and the approach remains experimental.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed diagnosis of thyroid cancer according to the 2022 WHO classification of thyroid tumors. Differentiated thyroid carcinoma must be diagnosed as radioactive iodine-refractory (RAIR) by a nuclear medicine specialist.
* Evidence of progressive disease based on RECIST 1.1 criteria in pre-treatment imaging.
* Prior surgical resection of resectable cervical lesions, with currently unresectable systemic disease.
* Previous targeted therapy was discontinued due to intolerance, or lack of benefit from targeted therapy assessed by investigator, or patient refusal.
* At least one measurable target metastatic lesion on contrast-enhanced CT/MRI (longest diameter of lesion ≥ 10 mm or shortest diameter of lymph node ≥ 15 mm).
* Positive CTR-FAPI uptake in lesions, defined as SUVmax \> 10 in more than half of the lesions on 68Ga-CTR-FAPI PET/CT.
* Life expectancy \> 6 months.
* ECOG performance status ≤ 2.
* Prior anti-tumor therapy-related toxicities that recoverd to Grade 0 or 1 (except alopecia, pigmentation, or chronic radiation toxicities and deemed irreversible by the investigator).
* For subjects with fertility: agreement to use effective contraception during treatment and 4 months (males) or 7 months (females) after the last dose.
* Voluntary participation and signed informed consent.

Exclusion Criteria:

* Presence of CTR-FAPI-negative lesions (i.e., malignant lesions on contrast-enhanced CT/MRI without uptake on 68Ga-CTR-FAPI PET/CT).
* Prior therapeutic radionuclide therapy (except 131I).
* Systemic anti-cancer therapy (including chemotherapy, targeted therapy, immunotherapy, radionuclide therapy, or anti-tumor traditional Chinese medicine) within 4 weeks before the first dose.
* Participation in another drug or device clinical trial within 4 weeks before the first dose.
* Insufficient major organ function.
* Severe or uncontrolled comorbidities.
* Presence of pleural effusion or ascites requiring intervention or judged uncontrolled by the investigator at screening.
* Active infection within 4 weeks before the first dose.
* Women who are pregnant, breastfeeding, or planning pregnancy.
* Known allergy to contrast agents.
* History of symptomatic central nervous system metastases.
* Other concurrent malignancies.
* Surgery under general anesthesia within 8 weeks before the first dose.
* History of acute coronary syndrome or stroke within 8 weeks before the first dose.
* Severe claustrophobia.
* Any other condition deemed inappropriate for participation by the investigator (e.g., poor compliance, inability to cooperate with treatment and follow-up).

Where this trial is running

Beijing and 1 other locations

• National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College — Beijing, China (RECRUITING)
• Peking Union Medical College Hospital — Beijing, China (RECRUITING)

Study contacts

• Principal investigator: Yansong Lin, M.D. — Peking Union Medical College Hospital
• Study coordinator: Ziren Kong, M.D.

Conditions: Thyroid Cancer, Thyroid cancer, Radionuclide therapy, CTR-FAPI