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CompletedNCT04904120TIMAR1Updated Nov 7, 2023

Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy

A Phase 1 interventional study of [203Pb]VMT01 and [68Ga]VMT02 in Melanoma (Skin), Melanoma Stage IV and Melanoma, Uveal, sponsored by Perspective Therapeutics. Completed at 1 site in United States. Open to participants aged 18 Years to 89 Years. Per ClinicalTrials.gov, last updated 2023-11-07.

Sponsored by Perspective Therapeutics · Phase 1, Interventional, and Diagnostic

Phase
Phase 1
Study type
Interventional
Enrollment
7
Allocation
Randomized
Ages
18 Years to 89 Years
Sex
All
01

Study 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.

Read the detailed description

This is a first-in-human study evaluating the suitability of [203Pb]VMT01 for SPECT/CT imaging and [68Ga]VMT02 for PET/CT imaging of MC1R-expressing metastatic melanoma. Study results will provide foundational data to develop imaging and dosing for future therapeutic trials of [212Pb]VMT01 for the treatment of metastatic melanoma.

The study will be a cross-over study with the participants serving as their own comparator. Participants with positive FDG-PET scans for stage IV (or inoperable stage III) metastatic melanoma will undergo SPECT/CT scans utilizing [203Pb]VMT01 followed a few weeks later by PET/CT scans utilizing [68Ga]VMT02, or vice versa. The order of the imaging agents will be randomly assigned.

02

Conditions studied

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

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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)
03

Who can participate

Ages eligible
18 Years to 89 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Diagnosed with Stage IV metastatic melanoma, or inoperable Stage III equivalent
  2. Baseline fluorodeoxyglucose (FDG)-PET scan available from within 30 days prior to date of enrollment
  3. Blood counts and metabolic results within protocol limits within 14 days prior to enrollment
  4. Ability to lie flat and still for a minimum of two hours for imaging
  5. 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
  6. Documented life expectancy of at least 3 months

Exclusion criteria

Exclusion Criteria:

  1. Active secondary malignancy
  2. Prior treatment (for any reason) with radioactive nuclides; imaging tracers are acceptable
  3. Pregnancy or breast feeding a child
  4. Uncontrolled infection
  5. Treatment with another investigational drug within 30 days prior to enrollment date
  6. Any treatment with BRAF inhibitors since the baseline FDG-PET scan or plans for such treatment during the study
  7. Kidney function not within protocol limits
  8. BMI>40 kg/m2
  9. History of a condition resulting in anaphylaxis or angioedema
04

Study design

Phase
Phase 1
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Single (Outcomes assessor)
Enrollment
7 participants (actual)

Study arms

  • Active comparator
    [203Pb]VMT01 first

    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

  • Active comparator
    [68Ga]VMT02 first

    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

  • Drug[203Pb]VMT01

    Diagnostic imaging radiopharmaceutical; by intravenous infusion

  • Drug[68Ga]VMT02

    Diagnostic imaging radiopharmaceutical; by intravenous infusion

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 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).

  2. Biodistribution of [68Ga]VMT02

    Biodistribution will be calculated by utilizing PET/CT scans.

    Time frame: 12 hours

  3. Biodistribution of [203Pb]VMT01

    Biodistribution will be calculated by utilizing SPECT/CT scans.

    Time frame: 24 hours

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

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

    Time frame: 24 hours

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

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

    Time frame: 24 hours

  6. Renal Excretion of [203Pb]VMT01

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

    Time frame: 24 hours

  7. Modeling of [203Pb]VMT01 Dosimetry

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

    Time frame: 24 hours

Secondary outcomes

  1. MC1R Expression Correlation Between Archived Tumor Tissue and Study Imaging

    Archived (previously collected) tumor tissue will be tested for MC1R expression and compared to study images obtained using MC1R targeted imaging agents, \[203Pb\]VMT01 and \[68Ga\]VMT02. The data will be assessed for an association between positive tissue and positive images.

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

  2. Cancer Site Correlation Between Standard of Care Imaging Compared to Study Imaging

    Sites of cancer detected previously by imaging will be compared to the presence or absence of positive imaging scans with the study agents, \[203Pb\]VMT01 and \[68Ga\]VMT02.

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

  3. 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

    For a given participant, dosimetry calculations will be compared between the two imaging agents with respect to cumulative absorbed dose of radiation.

    Time frame: Visit 1 (Day 1) and Visit 3 (Day 21-34) imaging

06

Study locations

1 site
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
07

References and documents

Individual participant data

Plan to share: Yes — All de-identified individual participant data (IPD) that underlies results in a peer-reviewed scientific publication will be shared.

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT04904120
Lead sponsor
Perspective Therapeutics
Collaborators
Mayo Clinic
Responsible party
Sponsor
First posted
May 27, 2021
Start date
Mar 5, 2021
Primary completion
Sep 20, 2022
Completion
Sep 20, 2022
Last update
Nov 7, 2023

Study contacts

Frances L Johnson, MD
principal investigator · Perspective Therapeutics
Geoffrey B Johnson, MD, PhD
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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