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A Safety Study of 212Pb-Pentixather Radioligand Therapy

Primary Purpose

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

Status

Not yet recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

212-Lead Pentixather

203-Lead Pentixather SPECT/CT

About this trial

This is an interventional treatment trial for Carcinoid Tumor Lung focused on measuring radioligand therapy, pentixather, Lead 203, Lead 212, alpha therapy, dosimetry

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

The University of Iowa Theranostics Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

212-Lead Pentixather

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Determine tumor response

Tumor response will be assessed using the Response Evaluation Criteria in Solid Tumours (RECIST, v 1.1).

Full Information

NCT ID

NCT05557708

First Posted

September 20, 2022

Last Updated

September 23, 2022

Sponsor

Yusuf Menda

Collaborators

National Institutes of Health (NIH), National Cancer Institute (NCI), Holden Comprehensive Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT05557708

Brief Title

A Safety Study of 212Pb-Pentixather Radioligand Therapy

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

July 1, 2024 (Anticipated)

Primary Completion Date

June 30, 2026 (Anticipated)

Study Completion Date

June 30, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Yusuf Menda

Collaborators

National Institutes of Health (NIH), National Cancer Institute (NCI), Holden Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

radioligand therapy, pentixather, Lead 203, Lead 212, alpha therapy, dosimetry

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

212-Lead Pentixather

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

212-Lead Pentixather

Intervention Description

Pentixather radiolabeled with 212-lead to target malignant cells with the CXCR4 ligand.

Intervention Type

Diagnostic Test

Intervention Name(s)

203-Lead Pentixather SPECT/CT

Intervention Description

Pentixather radiolabeled with 203-Lead to identify the CXCR4 ligand on the malignant lesions for dosimetric analysis and treatment planning.

Primary Outcome Measure Information:

Title

Determine the recommended phase 2 dose of 212-Lead Pentixather

Description

The recommended phase 2 dose is based on the number of dose limiting toxicities observed post-treatment.

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Determine the targeting of atypical pulmonary neuroendocrine tumor and/or neuroendocrine carcinoma lesions with 203-Lead Pentixather SPECT/CT

Description

The number of lesions identified with 203-Lead Pentixather SPECT/CT will compared to FDG PET/CT and diagnostic CT scans at baseline.

Time Frame

baseline

Title

Determine tumor response

Description

Tumor response will be assessed using the Response Evaluation Criteria in Solid Tumours (RECIST, v 1.1).

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yusuf Menda, MD

Phone

319-356-3214

yusuf-menda@uiowa.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Kellie Bodeker, Ph.D.

Phone

319-384-9425

kellie-bodeker@uiowa.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yusuf Menda, MD

Organizational Affiliation

University of Iowa

Official's Role

Principal Investigator

Facility Information:

Facility Name

The University of Iowa Theranostics Center

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yusuf Menda, MD

Phone

319-356-3214

yusuf-menda@uiowa.edu

First Name & Middle Initial & Last Name & Degree

Kristin Gaimari-Varner, RN

kristin-gaimari-varner@uiowa.edu

First Name & Middle Initial & Last Name & Degree

Yusuf Menda, MD

First Name & Middle Initial & Last Name & Degree

Stephen Graves, PhD

First Name & Middle Initial & Last Name & Degree

Chandrikha Chandrasekharan, MBBS

First Name & Middle Initial & Last Name & Degree

Joseph Dillon, MD

First Name & Middle Initial & Last Name & Degree

David Bushnell, MD

First Name & Middle Initial & Last Name & Degree

Michael Graham, MD, Ph.D.

First Name & Middle Initial & Last Name & Degree

Janet Pollard, MD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Citations:

PubMed Identifier

28744319

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.

Results Reference

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PubMed Identifier

35674738

Citation

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.

Results Reference

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PubMed Identifier

35312939

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.

Results Reference

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A Safety Study of 212Pb-Pentixather Radioligand Therapy

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