A Safety Study of 212Pb-Pentixather Radioligand Therapy

Carcinoma, Small-Cell Lung Clinical Trial

Official title:

Phase 1 Trial of Dosimetry Guided 212Pb-pentixather Radioligand Therapy in Patients With Atypical Lung Carcinoids and Neuroendocrine Carcinomas

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05557708
• Other study ID #: 202209363
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: July 1, 2024
• Est. completion date: June 30, 2028

Study information

• Verified date: November 2023
• Source: University of Iowa
• Contact: Yusuf Menda, MD
• Phone: 319-356-3214
• Email: yusuf-menda[@]uiowa.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a first-in-human clinical trial evaluating the safety of an alpha-radiation treatment (Lead-212 labelled Pentixather) in patients who have been diagnosed with, and previously treated, for atypical carcinoid lesions of the lung.

Description:

This is a study to determine what dose is acceptably safe for further testing.

In this study, participants are asked to:

• undergo SPECT/CT imaging with Lead-203 Pentixather (a radiotracer) to ensure the tumor lesions have the needed receptors

• undergo serial blood sampling for during and after the SPECT/CT scan for radiation and dosimetry calculations (to determine how much of the Lead-212 Pentixather to administer)

• receive up to 2 infusions of arginine & lysine as a kidney protectant

• receive up to 2 infusions of Lead-212 Pentixather, 6 weeks between each infusion

• undergo imaging at 3 months post treatment to determine disease response

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: June 30, 2028
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• ability to provide independent consent

• adequate bone marrow function (platelet count = 100,000; hemoglobin of = 10 g/dL; neutrophil count = 1,500 cells/mm3)

• adequate kidney function (creatinine clearance of = 50 mL/min using the Cockcroft-Gault equation

• adequate liver function (serum bilirubin = 3x the upper limit of normal, AST = 5x the upper limit of normal, and ALT = 5x the upper limit of normal)

• failed initial therapy or declined further therapy known to confer benefit

• have at least one lesion = 2 cm that is positive for CXCR4 as demonstrated by Lead-203 Pentixather SPECT/CT

Exclusion Criteria:

• major surgery within 4 weeks of consent

• antoher investigational agent within 4 weeks of consent

• uncontrolled illness including, but not limited to, ongoing or active infection that would necessitate a delay in therapy or cause a hospital admission, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, hepatic cirrhosis or severe impairment, or psychiatric illness/social situations that would limit compliance with study requirements.

• prior solid organ transplant

• cytotoxic or antineoplastic therapy within 21 days of consent (42 days for nitrosoureas)

• antibody therapy within the 21 days of consent

• allogenic bone marrow or stem cell transplant, or any stem cell infusion, within 84 days of consent

• pregnancy

• breastfeeding

• refusal to comply with birth control requirements during study

Related Conditions & MeSH terms

• Carcinoid Tumor
• Carcinoma
• Carcinoma, Small Cell
• Carcinoma, Small-Cell Lung
• Lung Neoplasms
• Neuroendocrine Tumors
• Small Cell Lung Carcinoma

Intervention

Drug:
• 212-Lead Pentixather
Pentixather radiolabeled with 212-lead to target malignant cells with the CXCR4 ligand.

Diagnostic Test:
• 203-Lead Pentixather SPECT/CT
Pentixather radiolabeled with 203-Lead to identify the CXCR4 ligand on the malignant lesions for dosimetric analysis and treatment planning.

Locations

Country	Name	City	State
United States	The University of Iowa Theranostics Center	Iowa City	Iowa

Sponsors (4)

Lead Sponsor	Collaborator
Yusuf Menda	Holden Comprehensive Cancer Center, National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Buck AK, Serfling SE, Lindner T, Hanscheid H, Schirbel A, Hahner S, Fassnacht M, Einsele H, Werner RA. CXCR4-targeted theranostics in oncology. Eur J Nucl Med Mol Imaging. 2022 Oct;49(12):4133-4144. doi: 10.1007/s00259-022-05849-y. Epub 2022 Jun 8. — View Citation

Schottelius M, Osl T, Poschenrieder A, Hoffmann F, Beykan S, Hanscheid H, Schirbel A, Buck AK, Kropf S, Schwaiger M, Keller U, Lassmann M, Wester HJ. [177Lu]pentixather: Comprehensive Preclinical Characterization of a First CXCR4-directed Endoradiotherapeutic Agent. Theranostics. 2017 Jun 11;7(9):2350-2362. doi: 10.7150/thno.19119. eCollection 2017. — View Citation

Serfling SE, Lapa C, Dreher N, Hartrampf PE, Rowe SP, Higuchi T, Schirbel A, Weich A, Hahner S, Fassnacht M, Buck AK, Werner RA. Impact of Tumor Burden on Normal Organ Distribution in Patients Imaged with CXCR4-Targeted [68Ga]Ga-PentixaFor PET/CT. Mol Imaging Biol. 2022 Aug;24(4):659-665. doi: 10.1007/s11307-022-01717-1. Epub 2022 Mar 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the recommended phase 2 dose of 212-Lead Pentixather	The recommended phase 2 dose is based on the number of dose limiting toxicities observed post-treatment.	3 months
Secondary	Determine the targeting of atypical pulmonary neuroendocrine tumor and/or neuroendocrine carcinoma lesions with 203-Lead Pentixather SPECT/CT	The number of lesions identified with 203-Lead Pentixather SPECT/CT will compared to FDG PET/CT and diagnostic CT scans at baseline.	baseline
Secondary	Determine tumor response	Tumor response will be assessed using the Response Evaluation Criteria in Solid Tumours (RECIST, v 1.1).	3 months