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RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

Targeted Alpha-Particle Therapy for Advanced Somatostatin Receptor Type 2 (SSTR2) Positive Neuroendocrine Tumors

A Phase I/IIa First-in-Human Study of [212Pb]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

This study is Phase I/IIa First-in-Human Study of \[212Pb\]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors

Who May Be Eligible (Plain English)

Who May Qualify: 1. Adult (ages ≥18) PRRT-naïve subjects with NETs by local pathology. 2. Locally advanced/unresectable or metastatic NETs. 3. Radiological evidence of measurable disease by RECIST v1.1 criteria on CT with contrast or MRI of the areas of tumor involvement within 60 days of enrollment. 4. Lesions must have shown radiological evidence of disease progression in the 12 months prior to enrollment. 5. Demonstration of lesional SSTR2 expression using an FDA-approved somatostatin receptor PET imaging agent, e.g. \[68Ga\]DOTATATE, \[64Cu\]DOTATATE, or \[68Ga\]DOTATOC, (SSTR2 positivity defined as uptake \> background liver) obtained and interpreted in accordance with product labeling and appropriate clinical use criteria within 12 months of enrollment. 6. ECOG Performance Status ≤ 1. 7. Subjects with HIV positivity are allowed if CD4 Count \> 350 cells/μL. 8. Concurrent Somatostatin Analog (SSA) Therapy use while on protocol therapy is allowed provided that the subject the subject must be able to tolerate withholding long-acting SSA therapy for a minimum of 28 days and short-acting SSA therapy for a minimum of 24 hours before the first and subsequent administrations of \[203Pb\]VMT-α-NET or \[212Pb\]VMT-α-NET 9. Progressive Disease on approved therapies other than radionuclide therapy. 10. Must have clinically demonstrated adequate catecholamine blockade if catecholamine-secreting pheochromocytoma/paraganglioma tumors are present. 11. Able to understand and sign willing to sign a consent form and comply with all study requirements. 12. Life expectancy \> 3 months. 13. Satisfactory organ function as determined by laboratory testing. 14. For females of reproductive potential: agree to use of highly effective contraception and refrain from donating eggs (ova, oocytes) for the purpose of reproduction starting from screening, during treatment, and for at least 6 months after the last dose of \[212Pb\]VMT-α-NET ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. Adult (ages ≥18) PRRT-naïve subjects with NETs by local pathology. 2. Locally advanced/unresectable or metastatic NETs. 3. Radiological evidence of measurable disease by RECIST v1.1 criteria on CT with contrast or MRI of the areas of tumor involvement within 60 days of enrollment. 4. Lesions must have shown radiological evidence of disease progression in the 12 months prior to enrollment. 5. Demonstration of lesional SSTR2 expression using an FDA-approved somatostatin receptor PET imaging agent, e.g. \[68Ga\]DOTATATE, \[64Cu\]DOTATATE, or \[68Ga\]DOTATOC, (SSTR2 positivity defined as uptake \> background liver) obtained and interpreted in accordance with product labeling and appropriate clinical use criteria within 12 months of enrollment. 6. ECOG Performance Status ≤ 1. 7. Subjects with HIV positivity are allowed if CD4 Count \> 350 cells/μL. 8. Concurrent Somatostatin Analog (SSA) Therapy use while on protocol therapy is allowed provided that the subject the subject must be able to tolerate withholding long-acting SSA therapy for a minimum of 28 days and short-acting SSA therapy for a minimum of 24 hours before the first and subsequent administrations of \[203Pb\]VMT-α-NET or \[212Pb\]VMT-α-NET 9. Progressive Disease on approved therapies other than radionuclide therapy. 10. Must have clinically demonstrated adequate catecholamine blockade if catecholamine-secreting pheochromocytoma/paraganglioma tumors are present. 11. Able to understand and sign informed consent and comply with all study requirements. 12. Life expectancy \> 3 months. 13. Satisfactory organ function as determined by laboratory testing. 14. For females of reproductive potential: agree to use of highly effective contraception and refrain from donating eggs (ova, oocytes) for the purpose of reproduction starting from screening, during treatment, and for at least 6 months after the last dose of \[212Pb\]VMT-α-NET 15. For males of reproductive potential: agree to use of condoms or other methods to ensure effective contraception with partner and refrain from donating sperm starting from screening, during treatment, and for at least 6 months after the last dose of \[212Pb\]VMT-α-NET Exclusion Criteria: 1. Known hypersensitivity to SSA, SSTR imaging agents or any of the excipients of \[212Pb\]VMT-α-NET. 2. Active secondary malignancy. 3. Pregnancy or breastfeeding a child. 4. Febrile illness within 48 hours of any scheduled \[212Pb\]VMT-α-NET administration should be rescheduled \> 48 hours after resolution of fever\]. 5. Treatment with another investigational medicinal product within 30 days of anticipated treatment. 6. Prior treatment with systemic PRRT based therapies (i.e., \[90Y\] DOTATATE/DOTATOC or \[177Lu\] DOTATATE) 7. Prior treatment with 90-Yttrium radioembolization must be completed at least 6 months prior to enrollment. 8. External beam radiation therapy must be completed at least 30 days prior to enrollment. 9. Prior treatment with systemic anticancer therapy must be completed at least 30 days prior to enrollment (except for SSAs in subjects with functional tumors). 10. Major surgery must be completed at least 30 days prior to enrollment. 11. Known brain metastases; unless these metastases have been treated and stabilized 6 months prior to enrollment and the subject has been off steroid support for at least 14 days prior to enrollment. 12. Recently diagnosed and active infections requiring a time-limited course of antifungals or antibiotics in the 3 days prior to enrollment. 13. Receipt of live attenuated vaccines in the 7 days prior to enrollment. 14. Grade 3 nausea/vomiting or diarrhea within 72 hours before the of first scheduled dose of \[212Pb\]VMT-α-NET despite adequate antiemetic and other supportive care 15. Known medical condition which would make this protocol unreasonably hazardous for the subject. 16. Medical history of a condition resulting in a severe allergic reaction such as anaphylaxis or angioedema to known components of the Investigational Medicinal Product or excipients. 17. Current abuse of alcohol or illicit drugs (exclusive of use of medically prescribed cannabinoids). 18. Existence of any medical or social issues likely to interfere with study conduct or that may cause increased risk to the subject or to others, e.g., lack of ability to follow radiation safety precautions. 19. QTc \> 450 milliseconds for males and females.

Treatments Being Tested

DRUG

[203Pb]VMT-α-NET

\[203Pb\]VMT-α-NET is administered by intravenous bolus injection for single-photon emission computed tomography imaging.

DRUG

[212Pb]VMT-α-NET

\[212Pb\]VMT-α-NET is administered by intravenous infusion for treatment of SSTR2 expressing neuroendocrine tumors.

Locations (17)

Mayo Clinic
Jacksonville, Florida, United States
Biogenix Molecular
Miami, Florida, United States
The University of Chicago
Chicago, Illinois, United States
University of Iowa
Iowa City, Iowa, United States
University of Kentucky
Lexington, Kentucky, United States
Johns Hopkins
Baltimore, Maryland, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
BAMF Health
Grand Rapids, Michigan, United States
Michigan Health Professionals
Troy, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Washington University
St Louis, Missouri, United States
Nebraska Cancer Specialists
Omaha, Nebraska, United States
University of North Carolina
Chapel Hill, North Carolina, United States
Ohio State University
Columbus, Ohio, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
Virginia Cancer Specialists
Fairfax, Virginia, United States
Fred Hutchinson Cancer Center
Seattle, Washington, United States