Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy

NCT04904120 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: TIMAR1
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The study hypothesis is that new imaging agents \[203Pb\]VMT01 and \[68Ga\]VMT02 can be safely used in humans without independent biological effect and can be used to image melanoma tumors expressing the melanocortin sub-type 1 receptor (MC1R) by SPECT/CT and PET/CT imaging modalities respectively.

Conditions

Melanoma (Skin); Melanoma Stage IV; Melanoma, Uveal; Melanoma, Mucosal

Keywords

Melanoma; Theranostic; Radiopharmaceutical; Radiotherapy; Alpha-Particle; Diagnostic; Metastatic; Single Photon Emission Computed Tomography (SPECT); Positron Emission Tomography (PET); Melanocortin Receptor Sub-type 1 (MC1R); VMT01; VMT02; Pb-203; Ga-68; Cancer; Immunohistochemistry (IHC)

Outcome Measures

Primary Outcomes (7)

• Number of Participants with Study Imaging Agent-Associated Adverse Events (AE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

  Adverse Events (AEs) will be assessed for severity according to CTCAE v5.0 and for relatedness to each of the investigative imaging agents (\[203Pb\]VMT01 and \[68Ga\]VMT02). Assessments attributed as possibly, probably, or definitely related to the imaging agent will be considered related.

  Visit 1 (Day 1) through Visit 5 (approximately Day 60 but could extend up to Day 108); ongoing Serious Adverse Events (SAE) will be followed for no longer than Day 65 or 30 days from the date of the SAE report (whichever is later).

• Biodistribution of [68Ga]VMT02

  Biodistribution will be calculated by utilizing PET/CT scans.

  12 hours

• Biodistribution of [203Pb]VMT01

  Biodistribution will be calculated by utilizing SPECT/CT scans.

  24 hours

• Peak Plasma Concentration (Cmax) of [203Pb]VMT01

  Cmax will be determined by blood sampling and direct radioactivity measurements.

  24 hours

• Area Under the Plasma Concentration Versus Time Curve (AUC) for [203Pb]VMT01

  AUC will be determined by blood sampling and direct radioactivity measurements.

  24 hours

• Renal Excretion of [203Pb]VMT01

  Renal excretion will be determined by urine sampling and direct radioactivity measurements.

  24 hours

• Modeling of [203Pb]VMT01 Dosimetry

  Dosimetry will be modeled by utilizing the SPECT/CT scans.

  24 hours

Secondary Outcomes (3)

• MC1R Expression Correlation Between Archived Tumor Tissue and Study Imaging

  Historical tissue sample (collected <365 days before study enrollment) compared to Visit 1 (Day 1) and Visit 3 (Day 21-34) imaging

• Cancer Site Correlation Between Standard of Care Imaging Compared to Study Imaging

  Historical imaging information compared to Visit 1 (Day 1) and Visit 3 (Day 21-34) imaging

• Dosimetry will be Calculated for each Study Imaging Agent by Measuring the Cumulative Absorbed Dose of Radiation to the Participant's Individual Organs and Tumors

  Visit 1 (Day 1) and Visit 3 (Day 21-34) imaging

Study Arms (2)

[203Pb]VMT01 first

ACTIVE COMPARATOR

Participants randomized to this arm will receive imaging agent \[203Pb\]VMT01 and undergo SPECT/CT imaging first. Later, participants in this arm will receive \[68Ga\]VMT02 and undergo PET/CT imaging.

Drug: [203Pb]VMT01; Drug: [68Ga]VMT02

[68Ga]VMT02 first

ACTIVE COMPARATOR

Participants randomized to this arm will receive imaging agent \[68Ga\]VMT02 and undergo PET/CT imaging first. Later, participants in this arm will receive \[203Pb\]VMT01 and undergo SPECT/CT imaging.

Drug: [203Pb]VMT01; Drug: [68Ga]VMT02

Interventions

[203Pb]VMT01 DRUG

Diagnostic imaging radiopharmaceutical; by intravenous infusion

[203Pb]VMT01 first; [68Ga]VMT02 first

[68Ga]VMT02 DRUG

Diagnostic imaging radiopharmaceutical; by intravenous infusion

[203Pb]VMT01 first; [68Ga]VMT02 first

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with Stage IV metastatic melanoma, or inoperable Stage III equivalent
• Baseline fluorodeoxyglucose (FDG)-PET scan available from within 30 days prior to date of enrollment
• Blood counts and metabolic results within protocol limits within 14 days prior to enrollment
• Ability to lie flat and still for a minimum of two hours for imaging
• Male and female participants with reproductive potential must agree to use highly effective contraception in preparation of the study, during the study, and for 4 weeks following the last dose of an investigative imaging agent
• Documented life expectancy of at least 3 months

You may not qualify if:

• Active secondary malignancy
• Prior treatment (for any reason) with radioactive nuclides; imaging tracers are acceptable
• Pregnancy or breast feeding a child
• Uncontrolled infection
• Treatment with another investigational drug within 30 days prior to enrollment date
• Any treatment with BRAF inhibitors since the baseline FDG-PET scan or plans for such treatment during the study
• Kidney function not within protocol limits
• BMI\>40 kg/m2
• History of a condition resulting in anaphylaxis or angioedema

Sponsors & Collaborators

• Perspective Therapeutics: lead
• Mayo Clinic: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Melanoma; Uveal Melanoma; Disease; Neoplasm Metastasis; Neoplasms

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Study Officials

• Frances L Johnson, MD

  Perspective Therapeutics

  PRINCIPAL INVESTIGATOR

• Geoffrey B Johnson, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Archived tumor tissue will be tested for expression of the imaging target, melanocortin receptor sub-type 1 (MC1R). The qualified researcher who tests the sample, and the independent pathologist who reviews the results, will be blinded to a participant's identifying information and imaging results. Evaluators will not have access to the medical record. A pool of three qualified readers will evaluate study images (PET/CT and SPECT/CT). Images and medical information given to the readers will not include a participant's identifying information. The reader pool will not know the sequence of imaging for a participant or have access to the medical record. An independent medical physicist will validate imaging results and measurements of radiation absorbed and excreted by the participant's body. The physicist will be blinded to participant identifiers and demographics, as well as the sequence of imaging for a participant. The physicist will not have access to the medical record.
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2021
• First Posted: May 27, 2021
• Study Start: March 5, 2021
• Primary Completion: September 20, 2022
• Study Completion: September 20, 2022
• Last Updated: November 7, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)