Overview
This is a multicenter, randomized, open-label, non-inferiority Phase III clinical trial, aims to compare 68Ga-CTR-FAPI PET-CT-guided surgery to investigator-chosen surgical approaches to evaluate its efficacy in treating newly diagnosed medullary thyroid carcinoma. This study plans to enroll 150 newly diagnosed MTC patients, who will be randomly assigned in a 2:1 ratio to the experimental group (surgery based on 68Ga-CTR-FAPI PET-CT findings) and the control group (surgery based on the investigator's choice). The primary endpoint is the biochemical cure rate, with secondary endpoints including the biochemical cure rate in the R0 resection subgroup, the unnecessary dissection rate in the biochemical-cured subgroup, 3-year recurrence-free survival, the rate of change in surgical extent, and diagnostic accuracy.
Description
Medullary thyroid carcinoma (MTC) is a relatively difficult-to-treat malignant thyroid tumor with a wide range of metastases. Surgery is the only curative treatment, and accurate assessment of the extent of metastatic disease is crucial for planning the surgical extent. Conventional imaging modalities have limited utility in fully evaluating the extent of MTC involvement. The tumor microenvironment of MTC is rich in cancer-associated fibroblasts (CAFs), which highly express fibroblast activation protein (FAP), whereas normal tissue fibroblasts express little to no FAP. Given the co-localization relationship between MTC cells and CAFs, fibroblast activation protein inhibitors (FAPIs) targeting FAP can be used to localize MTC lesions. The molecular probe CTR-FAPI, developed through covalent modification, improved the detection rate and diagnostic accuracy for MTC, providing a theoretical basis for performing precise surgery for MTC based on the extent of disease revealed by 68Ga-CTR-FAPI PET-CT.
This is a multicenter, randomized, open-label, two-arm, non-inferiority Phase III clinical trial. This study plans to enroll 150 newly diagnosed MTC patients, who will be randomly assigned in a 2:1 ratio to the experimental group (surgery based on 68Ga-CTR-FAPI PET-CT findings) and the control group (surgery based on the investigator's choice).
The study hypothesizes that CTR-FAPI-guided surgery can identify and resect more positive lesions while avoiding prophylactic dissection of disease-free areas, thereby benefiting patients. Proving the benefit of the former requires complete resection of all positive lesions. However, due to the frequent local invasion and adhesions associated with MTC lesions, achieving R0 resection is difficult in some patients. Therefore, the primary objective is to demonstrate that CTR-FAPI-guided surgery is non-inferior to the investigator's choice in IIT population. The primary endpoint was biochemical cure rate at 1-month post-surgery, defined by normalization of serum calcitonin levels. This parameter represents the strictest curative level for MTC and correlates with survival outcomes. In a nationwide retrospective analysis involving 863 patients, the 10-year overall survival (OS) of biochemical-cured MTC was 97.7%; in comparison, the 10-year OS of non-cured MTC was 70.3%.
The secondary objectives are to demonstrate its superiority in the subgroup achieving R0 resection, and to show that it avoids unnecessary lateral neck/upper mediastinum dissection in the subgroup achieving biochemical-cure. Key secondary endpoints include: the biochemical cure rate at 1 month post-surgery in the R0 resection subgroup, and the unnecessary dissection rate in the biochemical-cured subgroup, which address the two important secondary objectives and the study hypothesis. Other secondary endpoints include: 3-year recurrence-free survival, the rate of surgical plan modification in the experimental group, and the diagnostic accuracy of different imaging modalities for MTC lesions.
Eligibility
Inclusion Criteria:
- Newly-diagnosed medullary thyroid carcinoma meeting either criterion a or criteria b + c:
- Pathologically or cytologically confirmed diagnosis;
- Elevated serum calcitonin level (\>10 pg/mL);
- Other infectious or neoplastic diseases excluded.
- Life expectancy ≥ 12 weeks;
- ECOG performance status of 0 or 1;
- Absence of distant metastasis confirmed by conventional imaging, with resectable locoregional disease;
- Scheduled to undergo surgery within 30 days;
- Females of childbearing potential must use effective contraception (e.g., sterilization, intrauterine device, condoms, oral/injectable contraceptives, abstinence, or partner vasectomy) during the study and for 6 months after study completion. Male participants must agree to use effective contraception during the same period;
- Capable of understanding and voluntarily signing the informed consent form with good compliance.
Exclusion Criteria:
- History of prior treatment for medullary thyroid carcinoma (e.g., surgery, radiotherapy, targeted therapy, radionuclide therapy, or interventional therapy).
- Major organ dysfunction, defined as:
- Bone marrow impairment: WBC ≤ 4.0×10⁹/L or neutrophils ≤ 1.5×10⁹/L; platelets ≤ 100×10⁹/L; hemoglobin ≤ 90 g/L
- Hepatic impairment: PT or APTT ≥ 1.5 × ULN; total bilirubin ≥ 1.5 × ULN; ALT/AST ≥ 2.5 × ULN (or ≥ 5 × ULN in participants with liver metastases); ALP ≥ 2.5 × ULN (or ≥ 4.5 × ULN in cases with bone or liver metastases)
- Renal impairment: BUN ≥ 1.5 × ULN; serum creatinine ≥ 1.5 × ULN
- Women who are planning pregnancy, currently pregnant, or breastfeeding.
- History of other malignant tumors;
- Inability to lie flat for at least 30 minutes;
- Known allergy to contrast agents;
- Claustrophobia or other psychiatric disorders that may preclude compliance with study procedures;
- Unwillingness to participate in the clinical trial;
- Assessed as not being a surgical candidate or refusal to undergo surgery;
- Any other condition deemed by the investigator to make the participant unsuitable for the study.
