Evaluation of 177Lu-DOTA-EB-FAPI in Patients With Metastatic Radioactive Iodine Refractory Thyroid Cancer

March 27, 2025 updated by: The First Affiliated Hospital of Xiamen University

An Open-Label, Non-Randomized, Dose Escalation, Single-Center, Investigator-Initiated Trial to Determine the Safety, Dosimetry, and Preliminary Effectiveness of 177Lu-DOTA-EB-FAPI in Metastatic Radioactive Iodine Refractory Thyroid Cancer Patients With Progressive Disease After Tyrosine Kinase Inhibitors Treatment

Increased fibroblast activation protein expression is positively correlated with the dedifferentiation and aggressiveness of thyroid cancer. Radiolabeled fibroblast activation protein inhibitor therapy, also known as radioligand therapy has become a novel treatment for patients with radioactive iodine refractory thyroid cancer and disease progression after first-line treatment. However, a major problem in the therapeutic use of 177Lu-DOTA-FAPI has been its short half-life and fast rate of clearance. This study was designed to evaluate the safety, tolerability, and maximum tolerated dose of a long-lasting radiolabeled fibroblast activation protein inhibitor 177Lu-DOTA-EB-FAPI in mRAIR-TC patients with PD after TKIs treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This dose-escalation study will include a maximum of 20 mRAIR-TC subjects with progressive disease after tyrosine kinases inhibitors (TKIs) treatment, with an increased radiotracer uptake in tumors on 68Ga-FAPI-46 PET/CT. The initial dose of 177Lu-DOTA-EB-FAPI is 2.22GBq (60 mCi), and subsequent cohorts receive an incremental 50% dose increase until dose-limiting toxicity (DLT) was observed. Treatment is planned for up to 2 cycles, and the time interval between cycles is 6 weeks. The primary endpoint assessed the safety and maximum tolerated dose of 177Lu-DOTA-EB-FAPI used for radioligand therapy in patients with advanced mRAIR-TC. Secondary endpoints included dosimetry and determination of the preliminary treatment efficacy of 177Lu-DOTA-EB-FAPI.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Xiamen, China, 361000
        • The First Affiliated Hospital of Xiamen University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Ability to understand and willingness to sign a written informed consent document.
  2. Age 18 and older
  3. Confirmed unresectable or metastatic radioactive iodine refractory thyroid cancer with measurable disease per RECIST (version 1.1) (i.e. at least 1 lesion > 1 cm or lymph node > 1.5 cm in short axis)
  4. Progressive disease after TKIs treatment
  5. Eastern Cooperative Oncology Group Performance Status ≤ 3
  6. Participant must have completed prior therapy at least 2 weeks (washout period) prior to 68Ga-FAPI-46 PET/CT scan. Any clinically significant toxicity (with the exceptions of hair loss and sensory neuropathy) related to prior therapy resolved below Grade 2 or baseline. Completion of entry into 68Ga-FAPI-46 study and completion of scan
  7. Hematologic parameters defined as:

Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 Platelet count ≥ 50,000/mm3 Hemoglobin ≥ 8 g/dL

Blood chemistry levels defined as:

AST, ALT, alkaline phosphatase ≤ 5 times upper limit of normal (ULN) Total bilirubin ≤ 3 times ULN Creatinine ≤ 3 times ULN Able to remain motionless for up to 30-60 minutes per scan

Exclusion Criteria:

  1. Participant on any chemical anticoagulant including antiplatelet agents (excluding ASA)
  2. Participants with Class 3 or 4 NYHA Congestive Heart Failure
  3. Clinically significant bleeding within two weeks prior to trial entry (e.g. gastrointestinal bleeding, intracranial bleeding)
  4. Pregnant or lactating women
  5. Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e. larger than what is required for placement of a central venous access, percutaneous feeding tube, or biopsy) within 28 days prior to study day 1 or anticipated surgery within the subsequent 6 weeks
  6. Has an additional active malignancy requiring therapy within the past 2 years
  7. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
  8. Psychiatric illness/social situations that would interfere with compliance with study requirements
  9. Cannot undergo PET/CT scanning because of weight limits (350 lbs)
  10. INR>1.2; PTT>5 seconds above UNL

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 177Lu-DOTA-EB-FAPI 1
177Lu-DOTA-EB-FAPI A maximum of 2 cycles of 60 mCi (2.22 GBq) 177Lu-DOTA-EB-FAPI, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 2 cycles, every 6 weeks
Drug: 177Lu-DOTA-EB-FAPI 1 radionuclide therapy
radionuclide therapy using 177Lu-DOTA-EB-FAPI 60 mCi (2.22 GBq) will be performed 6-weekly. A maximum of 2 cycles will be administered.
Experimental: 177Lu-DOTA-EB-FAPI 2
177Lu-DOTA-EB-FAPI A maximum of 2 cycles of 90mCi (3.33 GBq) 177Lu-DOTA-EB-FAPI, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 2 cycles, every 6 weeks
Drug: 177Lu-DOTA-EB-FAPI 2 radionuclide therapy
radionuclide therapy using 177Lu-DOTA-EB-FAPI 90 mCi (3.33 GBq) will be performed 6-weekly. A maximum of 2 cycles will be administered.
Experimental: 177Lu-DOTA-EB-FAPI 3
177Lu-DOTA-EB-FAPI A maximum of 2 cycles of 135 mCi (4.99 GBq) 177Lu-DOTA-EB-FAPI, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 2 cycles, every 6 weeks
Drug: 177Lu-DOTA-EB-FAPI 3 radionuclide therapy
radionuclide therapy using 177Lu-DOTA-EB-FAPI 135 mCi (4.99 GBq) will be performed 6-weekly. A maximum of 2 cycles will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine the maximum tolerated dose (MTD)
Time Frame: From date of involvement until 6 weeks after the second treatment cycles
The MTD is the dose level below that which 2 out of 6 subjects in a cohort have DLT
From date of involvement until 6 weeks after the second treatment cycles
Incidence of treatment-related adverse events (safety and tolerability)
Time Frame: From date of involvement until 6 weeks after the second treatment cycles
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. Dose-limiting toxicity was defined as any 177Lu-DOTA-EB-FAPI-related AE ≥ grade 3 (G3).
From date of involvement until 6 weeks after the second treatment cycles

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: baseline, 6 weeks after each treatment cycle
68Ga-Fibroblast activation protein inhibitor 46 will be performed for efficacy evaluation by RECIST 1.1. Particularly, 68Ga-FAPI-46 will be performed at baseline, and 6 weeks after each treatment cycle.
baseline, 6 weeks after each treatment cycle
Dosimetry
Time Frame: Dosimetry was estimated in the first treatment cycle for each patient
Dosimetry, measured as absorbed dose in tumor and normal organs (Gy/GBq), was estimated in the first treatment cycle for each patient.
Dosimetry was estimated in the first treatment cycle for each patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital of Xiamen University

Investigators

  • Study Chair: Haojun Chen, MD, PhD, The First Affiliated Hospital of Xiamen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2022

Primary Completion (Actual)

June 15, 2024

Study Completion (Actual)

March 27, 2025

Study Registration Dates

First Submitted

June 5, 2022

First Submitted That Met QC Criteria

June 5, 2022

First Posted (Actual)

June 8, 2022

Study Record Updates

Last Update Posted (Actual)

April 1, 2025

Last Update Submitted That Met QC Criteria

March 27, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XMYY-2022KY054

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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