Clinical Evaluation of 177Lu-AB-3PRGD2 in Various Solid Tumors With Integrin αvβ3 Positive Expression

Refractory Solid Tumor Clinical Trial

Official title:

An Open-Label, Non-Randomized, Single-Center, Investigator-Initiated Trial to Determine the Effectiveness of 177Lu-AB-3PRGD2 in Various Solid Tumors With Integrin αvβ3 Positive Expression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06375564
• Other study ID #: XMYY-2020KY067-05
• Status: Recruiting
• Phase: Phase 1
• Start date: June 12, 2024
• Est. completion date: December 30, 2026

Study information

• Verified date: April 2024
• 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

This is an open-label, non-controlled, non-randomized study to assess the therapeutic efficacy of 177Lu-AB-3PRGD2 in patients with various solid tumors who will undergo radioligand therapy using 177Lu-AB-3PRGD.

Description:

Integrin αvβ3 is highly expressed in some tumor cells and neovascularization, which is an ideal target for diagnosis and treatment of solid tumors. 177Lu-AB-3PRGD2, is a kind of new drug based on independent research and development in China, providing an effective target for the treatment of tumors. All patients underwent whole-body 68Ga-RGD PET/CT for selection and accepted intravenous injection with a fixed dose of 2.96 GBq (80 mCi) of 177Lu-AB-3PRGD2 within one week. Treatment is planned for up to 4 cycles, and the time interval between cycles is 6 weeks. The primary endpoint assessed the preliminary treatment efficacy of 177Lu-AB-3PRGD2 used for radioligand therapy in patients with various advanced tumors. The secondary endpoint evaluates the safety of 177Lu-AB-3PRGD2.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 30, 2026
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

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

2. Age 18 and older.

3. 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).

4. Progressive disease after multiple-lines treatment.

5. Eastern Cooperative Oncology Group Performance Status = 3.

6. Participant must have completed prior therapy at least 2 weeks (washout period) before 68Ga-RGD 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-RGD study and completion of the scan.

7. Hematologic parameters are defined as Absolute neutrophil count (ANC) = 1000 cells/mm3 Platelet count = 50,000/mm3 Hemoglobin = 8 g/dL.

8. 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:

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 before 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 before 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.

Related Conditions & MeSH terms

• Neoplasms
• Refractory Solid Tumor

Intervention

Drug:
• 177Lu-AB-3PRGD2 radioligand therapy
Radioligand therapy using 177Lu-AB-3PRGD2 80 mCi (2.96 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	Objective response rate (ORR)	68Ga-RGD will be performed for efficacy evaluation by RECIST 1.1. Particularly, 68Ga-RGD will be performed at baseline, and 6 weeks after two treatment cycles.	At the end of Cycle 4 (each cycle is 42 days)
Secondary	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-AB-3PRGD2-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 4 (each cycle is 42 days)