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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Refractory Solid Tumor
• Intervention / Treatment: Drug: 177Lu-DOTA-EB-FAPI radionuclide therapy

Detailed 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 3.7GBq (100 mCi). 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 various advanced tumors. Secondary endpoints included dosimetry and determination of the preliminary treatment efficacy of 177Lu-DOTA-EB-FAPI.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Hao Fu, MD, PhD; Phone Number: +8615959230059; Email: fuhaonuclear@163.com
• Study Contact Backup: Name: Jingxiong Huang, MD.; Phone Number: +8613806082344; Email: huang_hjx9@126.com

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361000
      • Recruiting
      • The First Affiliated Hospital of Xiamen University
      • Contact: Jingxiong Huang, MD; Phone Number: +8613806082344; Email: huang_hjx9@126.com
      • Principal Investigator: Jingxiong Huang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 177Lu-DOTA-EB-FAPI; 177Lu-DOTA-EB-FAPI A maximum of 2 cycles of 100 mCi (3.7 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 radionuclide therapy; radionuclide therapy using 177Lu-DOTA-EB-FAPI 100 mCi (3.7 GBq) will be performed 6-weekly. A maximum of 2 cycles will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Xiamen University

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2023
• Primary Completion (Estimated): December 15, 2024
• Study Completion (Estimated): June 15, 2025

Study Registration Dates

• First Submitted: July 17, 2023
• First Submitted That Met QC Criteria: July 26, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Radioligand therapy; 177Lu-DOTA-EB-FAPI; Refractory solid tumor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: XMFHIIT-2023KY037

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No