177Lu-CTR-FAPI for the Treatment of Thyroid Cancer

Official title

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

Overview

This is a multi-center, open-label, single-arm, dose-escalation phase I study, aiming to evaluate the safety and efficacy of 177Lu-CTR-FAPI (covalent targeted radioligand-fibroblast activation protein inhibitor), a novel radiopharmaceutical in the treatment of thyroid cancer. The primary endpoint of the study is the safety of 177Lu-CTR-FAPI, and the secondary endpoints include treatment response and dosimetry evaluation.

Detailed description

This clinical trial aims to evaluate the safety, tolerability, and preliminary efficacy of 177Lu-CTR-FAPI in patients with thyroid cancer. The study is designed to characterize the safety profile and dose-limiting toxicities (DLTs) in order to determine the maximum tolerated dose (MTD) of 177Lu-CTR-FAPI. Additionally, the study will assess biochemical responses, radiological responses and improvement of life quality as well as the dosimetry profile of this molecule.

This is a multi-center, open-label, single-arm phase I trial using a classic "3+3" dose-escalation design. The starting dose is 100 mCi and increases in 50 mCi increments for subsequent cohort. The MTD is defined as the highest dose at which fewer than 33% of participants experience a DLT during the 6-week observation period following the first administration. A total of 12 eligible participants with thyroid cancer will be enrolled and receive intravenous infusions of 177Lu-CTR-FAPI every 6 weeks, for up to 4 cycles. Dose delays are permitted based on evaluation of treatment response or the necessity for recovery from adverse reactions, with a maximum delay of 12 weeks after the previous dose.

Interventions

• Drug 177Lu-CTR-FAPI therapy
  177Lu-CTR-FAPI will be diluted in 100 mL of normal saline and administered via slow intravenous infusion over 20-30 minutes. Dose will be escalated according to a "3+3" design, starting at 100 mCi and increasing in 50 mCi increments for subsequent cohort. Vital signs will be measured before and after drug administration. Throughout the infusion period, subjects will be closely monitored for any associated symptoms and adverse reactions.

Primary outcome measures

• Incidence and severity of adverse events, frequency of dose-limiting toxicities and maximum tolerated dose of 177Lu-CTR-FAPI in patients with thyroid cancer. [Time frame: From enrollment to 6 weeks after the first injection of 177Lu-CTR-FAPI.]

Secondary outcome measures (10)

• Biochemical response rate [Time frame: From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.]
• Duration of biochemical response [Time frame: From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.]
• Radiological response rate [Time frame: From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.]
• Duration of radiological response [Time frame: From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.]
• Progression-free survival [Time frame: From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.]
• Overall survival [Time frame: From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.]
• Change of quality of life score [Time frame: From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.]
• Change of Pain score [Time frame: From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.]
• The absorbed doses for major organs and tumors of 177Lu-CTR-FAPI [Time frame: From enrollment to 8 days after the first administration]
• The maximum dose [Time frame: From enrollment to 8 days after the first administration]

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chine — Beijing
• Peking Union Medical College Hospital — Beijing

Publications

• Kong Z, Li Z, Cui XY, Wang J, Xu M, Liu Y, Chen J, Ni S, Zhang Z, Fan X, Huang J, Lin Y, Sun Y, He Y, Lin X, Meng T, Li H, Song Y, Peng B, An C, Gao C, Li N, Liu C, Zhu Y, Yang Z, Liu Z, Liu S. CTR-FAPI PET Enables Precision Management of Medullary Thyroid Carcinoma. Cancer Discov. 2025 Feb 7;15(2):316-328. doi: 10.1158/2159-8290.CD-24-0897. PMID 39470165
• Cui XY, Li Z, Kong Z, Liu Y, Meng H, Wen Z, Wang C, Chen J, Xu M, Li Y, Gao J, Zhu W, Hao Z, Huo L, Liu S, Yang Z, Liu Z. Covalent targeted radioligands potentiate radionuclide therapy. Nature. 2024 Jun;630(8015):206-213. doi: 10.1038/s41586-024-07461-6. Epub 2024 May 22. PMID 38778111

Identifiers

NCT: NCT07438847 · BRP-010-003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗