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

Primary Purpose

Refractory Thyroid Gland Carcinoma, Refractory Thyroid Gland Papillary Carcinoma, Refractory Thyroid Gland Follicular Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
177Lu-DOTA-EB-FAPI 1 radionuclide therapy
177Lu-DOTA-EB-FAPI 2 radionuclide therapy
177Lu-DOTA-EB-FAPI 3 radionuclide therapy
Sponsored by
The First Affiliated Hospital of Xiamen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Thyroid Gland Carcinoma focused on measuring radioactive iodine refractory thyroid cancer, RAIR-TC, radioligand therapy, 177Lu-DOTA-EB-FAPI

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Ability to understand and willingness to sign a written informed consent document.
  2. Age 18 or more years
  3. 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)
  4. Eastern Cooperative Oncology Group Performance Status ≤ 2
  5. 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
  6. 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:

  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

Sites / Locations

  • The First Affiliated Hospital of Xiamen UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

177Lu-DOTA-EB-FAPI 1

177Lu-DOTA-EB-FAPI 2

177Lu-DOTA-EB-FAPI 3

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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).
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

Secondary Outcome Measures

Objective response rate (ORR)
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.
Dosimetry
Dosimetry, measured as absorbed dose in tumor and normal organs (Gy/GBq), was estimated in the first treatment cycle for each patient.

Full Information

First Posted
June 5, 2022
Last Updated
July 9, 2023
Sponsor
The First Affiliated Hospital of Xiamen University
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1. Study Identification

Unique Protocol Identification Number
NCT05410821
Brief Title
Evaluation of 177Lu-DOTA-EB-FAPI in Patients With Metastatic Radioactive Iodine Refractory Thyroid Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 15, 2022 (Actual)
Primary Completion Date
June 15, 2024 (Anticipated)
Study Completion Date
June 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital of Xiamen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
classic 3+3 dose escalation
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
177Lu-DOTA-EB-FAPI 1
Arm Type
Experimental
Arm Description
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
Arm Title
177Lu-DOTA-EB-FAPI 2
Arm Type
Experimental
Arm Description
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
Arm Title
177Lu-DOTA-EB-FAPI 3
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
177Lu-DOTA-EB-FAPI 1 radionuclide therapy
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
177Lu-DOTA-EB-FAPI 2 radionuclide therapy
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
177Lu-DOTA-EB-FAPI 3 radionuclide therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of treatment-related adverse events (safety and tolerability)
Description
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).
Time Frame
From date of involvement until 6 weeks after the second treatment cycles
Title
To determine the maximum tolerated dose (MTD)
Description
The MTD is the dose level below that which 2 out of 6 subjects in a cohort have DLT
Time Frame
From date of involvement until 6 weeks after the second treatment cycles
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
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.
Time Frame
baseline, 6 weeks after each treatment cycle
Title
Dosimetry
Description
Dosimetry, measured as absorbed dose in tumor and normal organs (Gy/GBq), was estimated in the first treatment cycle for each patient.
Time Frame
Dosimetry was estimated in the first treatment cycle for each patient

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jingxiong Huang, MD
Phone
+8613806082344
Email
huang_hjx9@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hao Fu, MD, PhD
Phone
+8615959230059
Email
fuhaonuclear@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jingxiong Huang, MD
Organizational Affiliation
The First Affiliated Hospital of Xiamen University
Official's Role
Study Chair
Facility Information:
Facility Name
The First Affiliated Hospital of Xiamen University
City
Xiamen
ZIP/Postal Code
361000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jinxiong Huang
Phone
86 15980890201

12. IPD Sharing Statement

Learn more about this trial

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

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