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

NCT05410821 | Completed Phase 1

• 1 other identifier: XMYY-2022KY054
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Refractory Thyroid Gland Carcinoma; Refractory Thyroid Gland Papillary Carcinoma; Refractory Thyroid Gland Follicular Carcinoma; Refractory Thyroid Gland Hurthle Cell Carcinoma

Keywords

radioactive iodine refractory thyroid cancer; RAIR-TC; radioligand therapy; 177Lu-DOTA-EB-FAPI

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-related adverse events (safety and tolerability)

  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

• To determine the maximum tolerated dose (MTD)

  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

Secondary Outcomes (2)

• Objective response rate (ORR)

  baseline, 6 weeks after each treatment cycle

• Dosimetry

  Dosimetry was estimated in the first treatment cycle for each patient

Study Arms (3)

177Lu-DOTA-EB-FAPI 1

EXPERIMENTAL

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

177Lu-DOTA-EB-FAPI 2

EXPERIMENTAL

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

177Lu-DOTA-EB-FAPI 3

EXPERIMENTAL

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

Interventions

177Lu-DOTA-EB-FAPI 1 radionuclide therapy DRUG

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.

177Lu-DOTA-EB-FAPI 1

177Lu-DOTA-EB-FAPI 2 radionuclide therapy DRUG

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.

177Lu-DOTA-EB-FAPI 2

177Lu-DOTA-EB-FAPI 3 radionuclide therapy DRUG

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.

177Lu-DOTA-EB-FAPI 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and willingness to sign a written informed consent document.
• Age 18 and older
• 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)
• Progressive disease after TKIs treatment
• Eastern Cooperative Oncology Group Performance Status ≤ 3
• 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
• 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

You may not qualify if:

• Participant on any chemical anticoagulant including antiplatelet agents (excluding ASA)
• Participants with Class 3 or 4 NYHA Congestive Heart Failure
• Clinically significant bleeding within two weeks prior to trial entry (e.g. gastrointestinal bleeding, intracranial bleeding)
• Pregnant or lactating women
• 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
• Has an additional active malignancy requiring therapy within the past 2 years
• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
• Psychiatric illness/social situations that would interfere with compliance with study requirements
• Cannot undergo PET/CT scanning because of weight limits (350 lbs)
• INR\>1.2; PTT\>5 seconds above UNL

Sponsors & Collaborators

• The First Affiliated Hospital of Xiamen University: lead

Study Sites (1)

The First Affiliated Hospital of Xiamen University

Xiamen, 361000, China

Location

MeSH Terms

Conditions

Thyroid Neoplasms; Thyroid Cancer, Papillary; Adenocarcinoma, Follicular; Thyroid cancer, Hurthle cell

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Haojun Chen, MD, PhD

  The First Affiliated Hospital of Xiamen University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: classic 3+3 dose escalation

Study Record Dates

• First Submitted: June 5, 2022
• First Posted: June 8, 2022
• Study Start: June 15, 2022
• Primary Completion: June 15, 2024
• Study Completion: March 27, 2025
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)