Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Melanoma

Neoplasm Metastasis

Melanoma, Cutaneous Malignant

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neoplastic Processes

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Nivolumab

Immunomodulating Agents

Ipilimumab

Liver Extracts

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Liver SBRT following the second cycle of ipilimumab + nivolumab, which will then be continued up to 4 total cycles prior to subsequent maintenance nivolumab for duration of clinical benefit and tolerance (standard of care systemic therapy)

Ipilimumab administered IV over 85-100 minutes at 3 mg/kg (combined with nivolumab administered IV over 30-60 minutes at 1 mg/kg) every 3 weeks for a total of 4 doses or until progression or unacceptable toxicity.

Nivolumab administered IV over 30-60 minutes at 1 mg/kg (combined with ipilimumab administered IV over 85-100 minutes at 3 mg/kg) every 3 weeks for a total of 4 doses of the combination therapy or until progression or unacceptable toxicity. Subjects may receive maintenance dosing of nivolumab alone administered IV over 30-60 minutes at 240 mg every 2 weeks or 480 mg every 4 weeks for a maximum of 52 weeks or until progression or unacceptable toxicity.

24-45 Gy delivered in three fractions to up to 4 liver metastases

Stereotactic Body Radiation Therapy

Michael D. Green, MD, PhD

The primary purpose of this study is to determine the feasibility of liver stereotactic body radiation therapy (SBRT) given in combination with systemic therapy (ipilimumab and nivolumab) in adults with metastatic melanoma with liver metastases who are at significant risk of not benefiting from systemic therapy alone.

Hepatic Ablation of Melanoma Metastases to Enhance Immunotherapy Response, a Phase I Clinical Trial (HAMMER I)

Percentage of patients who receive all fractions of radiotherapy as planned following the second cycle of ipilimumab/nivolumab (I/N). Radiotherapy will be administered on C2D8 of I/N (±7days)

Proportion of patients who develop grade three or higher toxicities within 60 days after treatment with SBRT or thirty days after the last cycle of I/N, whichever occurs later. Any serious adverse event that occurs after this time frame and is considered related to the study treatment will also be reported.

OS defined as the time from start of treatment to death. This will be analyzed using Kaplan-Meier curves and descriptive statistics.

PFS defined as the time from start of treatment to date of radiological or clinical progression (leading to withdrawal from the study), or death from any cause, whichever comes first. Assessed Per RECIST v1.1; analyzed using Kaplan-Meier curves and descriptive statistics.

Freedom from local progression (local control) is defined as the lack of progression of the tumors treated by RT, either by tumor size or enhancement. Progression or development of new tumors elsewhere in the liver or outside of the liver would not constitute a local control failure. Tumors which increase in size or demonstrate new or increasing enhancement are considered progression. Analyzed using Kaplan-Meier curves and descriptive statistics.

The percentage of patients whose disease decreases (Partial response - PR) and/or disappears (Complete response - CR) after treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

The best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

University of Michigan Rogel Cancer Center

Oculocerebral Syndrome With Hypopigmentation

Radiopharmaceuticals

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.

Diagnostic imaging radiopharmaceutical; by intravenous infusion

[203Pb]VMT01

[68Ga]VMT02

Frances L Johnson, MD

Geoffrey B Johnson, MD, PhD

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.

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.

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.

Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy

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

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

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 will be calculated by utilizing PET/CT scans.

Biodistribution will be calculated by utilizing SPECT/CT scans.

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

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

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

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

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.

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.

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hepatic Ablation of Melanoma Metastases to Enhance Immunotherapy Response, a Phase I Clinical Trial (HAMMER I)	NCT05169957	Melanoma, Ocula... Melanoma, Cutan... Metastatic Mela... Melanoma, Mucos... Liver Metastase...	Ipilimumab Nivolumab Stereotactic Bo...	18 Years -	University of Michigan Rogel Cancer Center
Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy	NCT04904120	Melanoma (Skin) Melanoma Stage ... Melanoma, Uveal Melanoma, Mucos...	[203Pb]VMT01 [68Ga]VMT02	18 Years - 89 Years	Perspective Therapeutics
Hepatic Ablation of Melanoma Metastases to Enhance Immunotherapy Response, a Phase I Clinical Trial (HAMMER I)	NCT05169957	Melanoma, Ocula... Melanoma, Cutan... Metastatic Mela... Melanoma, Mucos... Liver Metastase...	Ipilimumab Nivolumab Stereotactic Bo...	18 Years -	University of Michigan Rogel Cancer Center

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