A Safety Study of 212Pb-Pentixather Radioligand Therapy

Early Phase 1

Not yet recruiting

• Conditions: Carcinoid Tumor Lung; Neuroendocrine Tumor of the Lung; Carcinoma, Small-Cell Lung
• Interventions: Drug: 212-Lead Pentixather; Diagnostic Test: 203-Lead Pentixather SPECT/CT

• Registration Number: NCT05557708
• Lead Sponsor: Yusuf Menda

Brief 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.

Detailed 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

Study Timeline

• Study First Submitted: 2022-09-20
• Study First Submitted QC: 2022-09-23
• Study First Posted: 2022-09-28
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-16
• Last Update Posted: 2023-11-18
• Study Start: 2024-07-01
• Primary Completion: 2026-06-30
• Study Completion: 2028-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
212-Lead Pentixather	203-Lead Pentixather SPECT/CT	Single intravenous infusion of Pentixather radiolabeled with Lead-212. Administered activity to participant is calculated from bone marrow and renal radiation constraints. Treatment is administered in 2 cycles with 6 weeks between the cycles.
212-Lead Pentixather	212-Lead Pentixather	Single intravenous infusion of Pentixather radiolabeled with Lead-212. Administered activity to participant is calculated from bone marrow and renal radiation constraints. Treatment is administered in 2 cycles with 6 weeks between the cycles.

Primary Outcome Measures

Name	Time	Method
Determine the recommended phase 2 dose of 212-Lead Pentixather	3 months	The recommended phase 2 dose is based on the number of dose limiting toxicities observed post-treatment.

Secondary Outcome Measures

Name	Time	Method
Determine the targeting of atypical pulmonary neuroendocrine tumor and/or neuroendocrine carcinoma lesions with 203-Lead Pentixather SPECT/CT	baseline	The number of lesions identified with 203-Lead Pentixather SPECT/CT will compared to FDG PET/CT and diagnostic CT scans at baseline.
Determine tumor response	3 months	Tumor response will be assessed using the Response Evaluation Criteria in Solid Tumours (RECIST, v 1.1).

Trial Locations

Locations (1)

The University of Iowa Theranostics Center; 🇺🇸 Iowa City, Iowa, United States