A Safety Study of 212Pb-Pentixather Radioligand Therapy

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Carcinoid Tumor Lung, Neuroendocrine Tumor of the Lung, Carcinoma, Small-Cell Lung

Intervention / Treatment
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* Drug: 212-Lead Pentixather
* Diagnostic Test: 203-Lead Pentixather SPECT/CT


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 212-Lead Pentixather<br>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. | Drug: 212-Lead Pentixather<br>* Pentixather radiolabeled with 212-lead to target malignant cells with the CXCR4 ligand.<br>Diagnostic Test: 203-Lead Pentixather SPECT/CT<br>* Pentixather radiolabeled with 203-Lead to identify the CXCR4 ligand on the malignant lesions for dosimetric analysis and treatment planning.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Determine tumor response | Tumor response will be assessed using the Response Evaluation Criteria in Solid Tumours (RECIST, v 1.1). | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radioligand therapy, pentixather, Lead 203, Lead 212, alpha therapy, dosimetry