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.

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

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

Data are obtained from protected health information. Only data from study participants who consented to data sharing will be shared.

Data type:

• patient demographics (age at consent, self-identified race ethnicity and gender, insurance status)
• tumor response (RECIST measures, imaging DICOM)
• adverse event logs indicating CTCAEv5 term and severity on a per-subject basis
• dosimetric analysis of 203-Lead Pentixather scans
• dose limiting toxicities: type and incidence
• diagnostic analysis of 203-Lead Pentixather and FDG PET/CT (or CT) scans

Protocol and ICF are made available upon request by email. All documents (Protocol, ICF, SAP, CSR, and analytic code) will be made available after primary objective is completed.

A materials transfer agreement or data usage agreement (depending upon the legal department's preference) will need to be fully executed prior to sharing.