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Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy (TIMAR1)

Primary Purpose

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

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

[203Pb]VMT01

[68Ga]VMT02

About this trial

This is an interventional diagnostic trial for Melanoma (Skin) focused on measuring 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)

Eligibility Criteria

18 Years - 89 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

[203Pb]VMT01 first

[68Ga]VMT02 first

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Biodistribution of [68Ga]VMT02

Biodistribution will be calculated by utilizing PET/CT scans.

Biodistribution of [203Pb]VMT01

Biodistribution will be calculated by utilizing SPECT/CT scans.

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

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

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

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

Renal Excretion of [203Pb]VMT01

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

Modeling of [203Pb]VMT01 Dosimetry

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

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT04904120

First Posted

May 3, 2021

Last Updated

May 5, 2023

Sponsor

Viewpoint Molecular Targeting

Collaborators

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT04904120

Brief Title

Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy

Acronym

TIMAR1

Official Title

A Phase 1 Cross-over Biodistribution Study of [203Pb]VMT01 for Single Photon Emission Computed Tomography (SPECT) Imaging and [68Ga]VMT02 for Positron Emission Tomography (PET) Imaging of Stage IV Metastatic Melanoma

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 5, 2021 (Actual)

Primary Completion Date

October 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Viewpoint Molecular Targeting

Collaborators

Mayo Clinic

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

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.

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.

6. Conditions and Keywords

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

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)

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

Outcomes Assessor

Masking Description

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.

Allocation

Randomized

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

[203Pb]VMT01 first

Arm Type

Active Comparator

Arm Description

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.

Arm Title

[68Ga]VMT02 first

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

[203Pb]VMT01

Intervention Description

Diagnostic imaging radiopharmaceutical; by intravenous infusion

Intervention Type

Drug

Intervention Name(s)

[68Ga]VMT02

Intervention Description

Diagnostic imaging radiopharmaceutical; by intravenous infusion

Primary Outcome Measure Information:

Title

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

Description

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).

Title

Biodistribution of [68Ga]VMT02

Description

Biodistribution will be calculated by utilizing PET/CT scans.

Time Frame

12 hours

Title

Biodistribution of [203Pb]VMT01

Description

Biodistribution will be calculated by utilizing SPECT/CT scans.

Time Frame

24 hours

Title

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

Description

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

Time Frame

24 hours

Title

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

Description

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

Time Frame

24 hours

Title

Renal Excretion of [203Pb]VMT01

Description

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

Time Frame

24 hours

Title

Modeling of [203Pb]VMT01 Dosimetry

Description

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

Time Frame

24 hours

Secondary Outcome Measure Information:

Title

MC1R Expression Correlation Between Archived Tumor Tissue and Study Imaging

Description

Time Frame

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

Title

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

Description

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

Title

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

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

89 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Frances L Johnson, MD

Organizational Affiliation

Viewpoint Molecular Targeting

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Geoffrey B Johnson, MD, PhD

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

All de-identified individual participant data (IPD) that underlies results in a peer-reviewed scientific publication will be shared.

Learn more about this trial

Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy

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