A Safety Study of 212Pb-Pentixather Radioligand Therapy

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Carcinoid Tumor Lung; Neuroendocrine Tumor of the Lung; Carcinoma, Small-Cell Lung
• Intervention / Treatment: Drug: 212-Lead Pentixather; Diagnostic test: 203-Lead Pentixather SPECT/CT

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yusuf Menda, MD; Phone Number: 319-356-3214; Email: yusuf-menda@uiowa.edu
• Study Contact Backup: Name: Kellie Bodeker, Ph.D.; Phone Number: 319-384-9425; Email: kellie-bodeker@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa Theranostics Center
      • Contact: Yusuf Menda, MD; Phone Number: 319-356-3214; Email: yusuf-menda@uiowa.edu
      • Contact: Kristin Gaimari-Varner, RN; Email: kristin-gaimari-varner@uiowa.edu
      • Principal Investigator: Yusuf Menda, MD
      • Sub-Investigator: Stephen Graves, PhD
      • Sub-Investigator: Chandrikha Chandrasekharan, MBBS
      • Sub-Investigator: Joseph Dillon, MD
      • Sub-Investigator: David Bushnell, MD
      • Sub-Investigator: Michael Graham, MD, Ph.D.
      • Sub-Investigator: Janet Pollard, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yusuf Menda
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH); Holden Comprehensive Cancer Center
• Investigators: Principal Investigator: Yusuf Menda, MD, University of Iowa

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: September 20, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: radioligand therapy; pentixather; Lead 203; Lead 212; alpha therapy; dosimetry
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Lung Neoplasms; Carcinoma; Small Cell Lung Carcinoma; Carcinoma, Small Cell; Neuroendocrine Tumors; Carcinoid Tumor
• Other Study ID Numbers: 202209363

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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

• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: A materials transfer agreement or data usage agreement (depending upon the legal department's preference) will need to be fully executed prior to sharing.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No