Clinical Evaluation of 177Lu-DOTA-EB-FAPI in Patients With Various Solid Tumors

Refractory Solid Tumor Clinical Trial

Official title:

An Open-Label, Non-Randomized, Single-Center, Investigator-Initiated Trial to Determine the Safety, Dosimetry, and Preliminary Effectiveness of 177Lu-DOTA-EB-FAPI in Patients With Various Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05963386
• Other study ID #: XMFHIIT-2023KY037
• Status: Recruiting
• Phase: Phase 1
• Start date: February 22, 2023
• Est. completion date: June 15, 2025

Study information

• Verified date: June 2023
• Source: The First Affiliated Hospital of Xiamen University
• Contact: Haojun Chen, MD, PhD
• Phone: +8618659285282
• Email: leochen0821[@]foxmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Increased fibroblast activation protein expression is positively correlated with the aggressiveness of cancer. Radiolabeled fibroblast activation protein inhibitor therapy, also known as radioligand therapy has become a novel treatment for patients with refractory cancer and disease progression after multiple-lines 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 and tolerabilityof a long-lasting radiolabeled fibroblast activation protein inhibitor 177Lu-DOTA-EB-FAPI in patients with various refractory solid tumors.

Description:

This IIT study will include a maximum of 20 subjects with progressive cancer after multiple-line treatment, with an increased radiotracer uptake in tumors on 68Ga-FAPI-46 PET/CT. The fixed dose of 177Lu-DOTA-EB-FAPI is 3.3GBq (90 mCi). Treatment is planned for up to 4 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 various advanced tumors. Secondary endpoints included dosimetry and determination of the preliminary treatment efficacy of 177Lu-DOTA-EB-FAPI.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 15, 2025
• Est. primary completion date: December 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Ability to understand and willingness to sign a written informed consent document.

• Age 18 and older.

• Confirmed unresectable or metastatic refractory 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 multiple-lines 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.

Related Conditions & MeSH terms

• Neoplasms
• Refractory Solid Tumor

Intervention

Drug:
• 177Lu-DOTA-EB-FAPI radionuclide therapy
radionuclide therapy using 177Lu-DOTA-EB-FAPI 90 mCi (3.3 GBq) will be performed 6-weekly. A maximum of 4 cycles will be administered.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Xiamen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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). For Hemoglobin < 8.0 g/dL; < 4.9 mmol/L; < 80 g/L; Need blood transfusion heal. Severe hypocytosis or with this age group The total number of normal cells was reduced >50% and =75%.	At the end of Cycle 2 (each cycle is 42 days)
Secondary	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 two treatment cycles.	At the end of Cycle 2 (each cycle is 42 days)
Secondary	Dosimetry	Dosimetry, measured as absorbed dose in tumor and normal organs (Gy/GBq), was estimated in the first treatment cycle for each patient.	At the end of Cycle 1 (each cycle is 42 days)