Thyroid Cancer
Conditions
Keywords
Thyroid cancer, Radionuclide therapy, CTR-FAPI
Brief summary
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
DRUG177Lu-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.
Sponsors
SHAOYAN LIU
Peking Union Medical College Hospital
Beijing Tsinghua Changgeng Hospital
Navy General Hospital, Beijing
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A total of 12 adult participants with thyroid cancer will receive intravenous infusions of 177Lu-CTR-FAPI every 6 weeks for up to 4 cycles. A standard "3+3" dose-escalation design is employed. The starting dose is 100 mCi, with subsequent dose levels increasing by 50 mCi increments. Dose delays are permitted based on recovery from adverse reactions and reatment response. Participants will undergo structured monitoring and follow-up visit to assess safety, efficacy, and long-term outcomes.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events, frequency of dose-limiting toxicities and maximum tolerated dose of 177Lu-CTR-FAPI in patients with thyroid cancer. | From enrollment to 6 weeks after the first injection of 177Lu-CTR-FAPI. | Incidence and severity of adverse events, frequency of dose-limiting toxicities(DLTs) will be evaluated within the 6-week observation period following the first administration of 177Lu-CTR-FAPI. DLTs will be assesse based on Common Terminology Criteria for Adverse Events (CTCAE) 5.0. The Maximum Tolerated Dose (MTD) will be 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical response rate | From enrollment to 1 year after the last 177Lu-CTR-FAPI injection. | Biochemical response of participants is deifined by the change of serum tumor markers (thyroglobulin for differentiated thyroid carcinoma and calcitonin for medullary thyroid carcinoma) from baseline as follows: Progressive disease (PD) is defined as more than 50% increase of serum tumor markers; Stable disease (SD) is defined as less than 50% increase or 50% reduction of serum tumor markers; Partial response (PR) is defined as more than 50% reduction of baseline serum tumor markers; Complete response (CR) is defined as normalization of serum tumor markers. The overall response rate (ORR) is measured as the proportion of participants achieving biochemical CR or PR, and the disease control rate (DCR) is defined as the proportion of participants achieving biochemical CR, PR, or SD. |
| Duration of biochemical response | From enrollment to 1 year after the last 177Lu-CTR-FAPI injection. | Duration of biochemical response is measured as the time period during which participants achieving biochemical CR or PR. |
| Radiological response rate | From enrollment to 1 year after the last 177Lu-CTR-FAPI injection. | The radiological response is evaluated by radiological examinations, including contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. The ORR is measured as the proportion of participants achieving CR or PR, and the DCR is defined as the proportion of participants achieving CR, PR, or SD. |
| Duration of radiological response | From enrollment to 1 year after the last 177Lu-CTR-FAPI injection. | Duration of radiological response is measured as the time period during which participants achieving radiological CR or PR. |
| Progression-free survival | From enrollment to 1 year after the last 177Lu-CTR-FAPI injection. | Progression-free survival (PFS) is defined as the time from enrollment until the first occurrence of disease progression or death from any cause, whichever occurs earlier. |
| Overall survival | From enrollment to 1 year after the last 177Lu-CTR-FAPI injection. | Overall survival (OS) is defined as the time from enrollment until death from any cause. |
| Change of quality of life score | From enrollment to 1 year after the last 177Lu-CTR-FAPI injection. | Change of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) scores compared with baseline is measured to evaluate improvement of life quality, in which a higher score of Function Scales and Global Health Status / Quality of Life Scale (transformed range 0-100) indicates better functioning or a higher quality of life and a lower score of Symptom Scales (transformed range 0-100) indicates less severity or frequency of the symptom. |
| Change of Pain score | From enrollment to 1 year after the last 177Lu-CTR-FAPI injection. | Change of Brief Pain Inventory (BPI) scores compared with baseline is measured to evaluate pain severity (range 0-10) and pain interference (range 0-10), and a lower score indicates a better outcome. |
| The absorbed doses for major organs and tumors of 177Lu-CTR-FAPI | From enrollment to 8 days after the first administration | After the first administration, participants will undergo radiation dosimetry assessments. Blood samples will be collected at specific time points for radioactivity measurements. Whole-body planar imaging as well as regional quantitative single photon emission computed tomography/computed tomography (SPECT/CT) at specific time points will also be performed. Regions of interest (ROI) will be delineated on SPECT images for lesions, kidneys, bone marrow, total skeleton, heart, liver, and spleen. These ROIs will be projected onto the whole-body images to derive time-activity curves and residence times. The OLINDA software will then be used to calculate the absorbed radiation doses in tumors and normal organs. |
| The maximum dose | From enrollment to 8 days after the first administration | The maximum dose will be acquired based on the organ dose limits calculated from the radiation dosimetry assessments. |
Countries
China
Contacts
CONTACTZiren Kong, M.D.
PRINCIPAL_INVESTIGATORYansong Lin, M.D.
Peking Union Medical College Hospital
PRINCIPAL_INVESTIGATORShaoyan Liu, M.D.
Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Outcome results
None listed