Back to results

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

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:

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

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

Sites / Locations

The First Affiliated Hospital of Xiamen UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

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

NCT ID

NCT05410821

First Posted

June 5, 2022

Last Updated

July 9, 2023

Sponsor

The First Affiliated Hospital of Xiamen University

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

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

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

Arm Title

177Lu-DOTA-EB-FAPI 2

Arm Type

Experimental

Arm Description

Arm Title

177Lu-DOTA-EB-FAPI 3

Arm Type

Experimental

Arm Description

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

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

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

huang_hjx9@126.com

First Name & Middle Initial & Last Name or Official Title & Degree

Hao Fu, MD, PhD

Phone

+8615959230059

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

We'll reach out to this number within 24 hrs