RECRUITING

Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors

Conditions

Neuroendocrine Tumors Neuroendocrine Tumor of the Lung Neuroendocrine Tumor of Pancreas Neuroendocrine Carcinoma Metastatic Neuroendocrine Tumor Carcinoid Carcinoid Tumor of GI System Carcinoid Tumor Paraganglioma Pheochromocytoma Small-cell Lung Cancer Radiopharmaceuticals SSTR Metastatic Neuroendocrine Tumors Lead-212 Pb-212 Theranostics Alpha Particle Therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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

Quick Facts

Study Start:2023-09-27

Study Completion:2029-12-26

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05636618

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 90 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Adult (ages ≥18) 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, i.e.\[68Ga\]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 0-2. 7. Subjects with HIV positivity are allowed if CD4 Count \> 500 cells/μL. 8. Concurrent SSA use while on protocol therapy is allowed provided that the subject: 1) has a functional tumor and 2) has previously demonstrated radiographic disease progression while on SSA therapy. 9. Long-acting somatostatin analogues are allowed but should be withheld within 30 days prior to \[68Ga\]DOTATATE PET/CT (or another SSTR2-PET), if clinically possible. Short acting somatostatin analogues should be withheld for 24 hours. 10. Progressive Disease on approved therapies other than radionuclide therapy. 11. Must have clinically demonstrated adequate catecholamine blockade if catecholamine-secreting pheochromocytoma/paraganglioma tumors are present. 12. Able to sign informed consent and comply with all study requirements. 13. Life expectancy \> 3 months.	1. Known hypersensitivity to Octreotate, DOTATATE, 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 drug product (therapeutic IND agents) 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-Ytrium 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 of first scheduled dose 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 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. 20. Abnormal laboratory values: * Hemoglobin ≤ 9.0 g/dL * Platelet Count ≤ 60,000/mm3 * Absolute Neutrophil Count (ANC) ≤ 1,250/mm3 * Calculated Creatinine Clearance \< 60 mL/min \OR Total Bilirubin ≥ 2.0 x ULN\\* * Albumin ≤ 2.8 g/dL * AST/ALT ≥ 3.0 x ULN

Inclusion Criteria

Exclusion Criteria

1. Adult (ages ≥18) 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, i.e.\[68Ga\]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 0-2.
7. Subjects with HIV positivity are allowed if CD4 Count \> 500 cells/μL.
8. Concurrent SSA use while on protocol therapy is allowed provided that the subject: 1) has a functional tumor and 2) has previously demonstrated radiographic disease progression while on SSA therapy.
9. Long-acting somatostatin analogues are allowed but should be withheld within 30 days prior to \[68Ga\]DOTATATE PET/CT (or another SSTR2-PET), if clinically possible. Short acting somatostatin analogues should be withheld for 24 hours.
10. Progressive Disease on approved therapies other than radionuclide therapy.
11. Must have clinically demonstrated adequate catecholamine blockade if catecholamine-secreting pheochromocytoma/paraganglioma tumors are present.
12. Able to sign informed consent and comply with all study requirements.
13. Life expectancy \> 3 months.

1. Known hypersensitivity to Octreotate, DOTATATE, 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 drug product (therapeutic IND agents) 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-Ytrium 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 of first scheduled dose 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 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.
20. Abnormal laboratory values:
* Hemoglobin ≤ 9.0 g/dL
* Platelet Count ≤ 60,000/mm3
* Absolute Neutrophil Count (ANC) ≤ 1,250/mm3
* Calculated Creatinine Clearance \< 60 mL/min \*OR Total Bilirubin ≥ 2.0 x ULN\*\*
* Albumin ≤ 2.8 g/dL
* AST/ALT ≥ 3.0 x ULN

Contacts and Locations

Study Contact

Markus Puhlmann, MD, MBA

CONTACT

(319) 665-2150

mpuhlmann@perspectivetherapeutics.com

Study Locations (Sites)

Mayo Clinic

Jacksonville, Florida, 32224

United States

Biogenix Molecular

Miami, Florida, 33165

United States

The University of Chicago

Chicago, Illinois, 60637

United States

University of Iowa

Iowa City, Iowa, 52242

United States

University of Kentucky

Lexington, Kentucky, 40536

United States

Johns Hopkins

Baltimore, Maryland, 21287

United States

BAMF Health

Grand Rapids, Michigan, 49503

United States

Michigan Health Professionals

Troy, Michigan, 48098

United States

Mayo Clinic

Rochester, Minnesota, 55905

United States

Washington University

Saint Louis, Missouri, 63110

United States

Nebraska Cancer Specialists

Omaha, Nebraska, 68130

United States

Virginia Cancer Specialists

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Perspective Therapeutics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-09-27

Study Completion Date2029-12-26

Study Record Updates

Study Start Date2023-09-27

Study Completion Date2029-12-26

Terms related to this study

Keywords Provided by Researchers

Radiopharmaceuticals
SSTR
Neuroendocrine Tumors
Carcinoid Tumor
Metastatic Neuroendocrine Tumors
Lead-212
Pb-212
Theranostics
Alpha Particle Therapy

Additional Relevant MeSH Terms

Neuroendocrine Tumors
Neuroendocrine Tumor of the Lung
Neuroendocrine Tumor of Pancreas
Neuroendocrine Carcinoma Metastatic
Neuroendocrine Tumor Carcinoid
Carcinoid Tumor of GI System
Carcinoid Tumor
Paraganglioma
Pheochromocytoma
Small-cell Lung Cancer