Treatment Using 177Lu-DOTA-EB-FAPI in Patients With Radioactive Iodine Refractory Thyroid Cancer
Study Details
Study Description
Brief Summary
This is an open-label, non-control, non-randomized study to investigate the long-lasting radiolabeled fibroblast activation protein inhibitor based radioligand therapy and evaluate response to 177Lu-DOTA-EB-FAPI in patients with radioactive iodine refractory thyroid cancer. A maximum of 3 cycles of various doses with 1.11GBq (30 mCi), 2.22GBq (60mCi), and 3.33GBq (90 mCi) of 177Lu-DOTA-EB-FAPI will be injected intravenously separately. All patients will undergo 68Ga-FAPI-46 and 18F-FDG PET/CT scans before and after the treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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 compare the efficacy of various doses of a long-lasting radiolabeled fibroblast activation protein inhibitor 177Lu-DOTA-EB-FAPI in patients with radioactive iodine refractory thyroid cancer.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 177Lu-DOTA-EB-FAPI 1 177Lu-DOTA-EB-FAPI A maximum of 3 cycles of 30 mCi (1.11GBq) 177Lu-DOTA-EB-FAPI, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 3 cycles, every 8 weeks |
Drug: 177Lu-DOTA-EB-FAPI 1 radionuclide therapy
radionuclide therapy using 177Lu-DOTA-EB-FAPI 30 mCi (1.11GBq) will be performed 8-weekly. A maximum of 3 cycles will be administered.The Amino-Acid Solution (AAS) to be used in this study, infused over 4-6 h, starting 30 min before radionuclide therapy.
Other Names:
|
| Experimental: 177Lu-DOTA-EB-FAPI 2 177Lu-DOTA-EB-FAPI A maximum of 3 cycles of 60 mCi (2.22GBq) 177Lu-DOTA-EB-FAPI, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 3 cycles, every 8 weeks |
Drug: 177Lu-DOTA-EB-FAPI 2 radionuclide therapy
radionuclide therapy using 177Lu-DOTA-EB-FAPI 60 mCi (2.22GBq) will be performed 8-weekly. A maximum of 3 cycles will be administered.The Amino-Acid Solution (AAS) to be used in this study, infused over 4-6 h, starting 30 min before radionuclide therapy.
Other Names:
|
| Experimental: 177Lu-DOTA-EB-FAPI 3 177Lu-DOTA-EB-FAPI A maximum of 3 cycles of 90 mCi (3.33GBq) 177Lu-DOTA-EB-FAPI, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 3 cycles, every 8 weeks |
Drug: 177Lu-DOTA-EB-FAPI 3 radionuclide therapy
radionuclide therapy using 177Lu-DOTA-EB-FAPI 90 mCi (3.33GBq) will be performed 8-weekly. A maximum of 3 cycles will be administered.The Amino-Acid Solution (AAS) to be used in this study, infused over 4-6 h, starting 30 min before radionuclide therapy.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall response rate (ORR) [From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.]
68Ga-Fibroblast activation protein inhibitor 46 and 18F-fluorodeoxyglucose will be performed for efficacy evaluation by RECIST 1.1 and PERCIST. Particularly, 68Ga-FAPI-46 will be performed at baseline and beginning of each circle, and 2 weeks after the last treatment. 18F-FDG will be performed at baseline and 2 weeks after the last treatment.
- Incidence of treatment-related adverse events (safety and tolerability) [From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months]
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Secondary Outcome Measures
- Progression-free survival [baseline, every 8 weeks up to 1 year after last patient first treatment]
Progression-free survival is defined as the time from the date of first dose to the date of the first documented radiological progression or death due to any cause
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Ability to understand and willingness to sign a written informed consent document.
-
Age 18 or more years
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Confirmed presence of 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)
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Eastern Cooperative Oncology Group Performance Status ≤ 2
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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 to Grade 1 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 ≥ 100,000/mm3 Hemoglobin ≥ 8 g/dL
Blood chemistry levels defined as:
AST, ALT, alkaline phosphatase ≤ 5 times upper limit of normal (ULN) Total bilirubin ≤ 2 times ULN Creatinine ≤ 2 times ULN Anticipated life expectancy ≥ 6 months Able to remain motionless for up to 30-60 minutes per scan
Exclusion Criteria:
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Participant on any chemical anticoagulant including antiplatelet agents (excluding ASA)
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Participants with Class 3 or 4 NYHA Congestive Heart Failure
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Clinically significant bleeding within two weeks prior to trial entry (e.g. gastrointestinal bleeding, intracranial bleeding)
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Pregnant or lactating women
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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
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Has an additional active malignancy requiring therapy within the past 2 years
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Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
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Psychiatric illness/social situations that would interfere with compliance with study requirements
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Cannot undergo PET/CT scanning because of weight limits (350 lbs)
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INR>1.2; PTT>5 seconds above UNL
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affiliated Hospital of Xiamen University | Xiamen | China | 361000 |
Sponsors and Collaborators
- The First Affiliated Hospital of Xiamen University
Investigators
- Study Chair: Jingxiong Huang, MD, The First Affiliated Hospital of Xiamen University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- XMYY-2022KY054