Trial Title:
Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors
NCT ID:
NCT05636618
Condition:
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
Conditions: Official terms:
Neoplasms
Small Cell Lung Carcinoma
Neuroendocrine Tumors
Carcinoid Tumor
Carcinoma, Neuroendocrine
Pheochromocytoma
Paraganglioma
Pancreatic Neoplasms
Lung Neoplasms
Digestive System Neoplasms
Gastrointestinal Neoplasms
Conditions: Keywords:
Radiopharmaceuticals
SSTR
Neuroendocrine Tumors
Carcinoid Tumor
Metastatic Neuroendocrine Tumors
Lead-212
Pb-212
Theranostics
Alpha Particle Therapy
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
A Phase I/IIa First-in-Human Study of [212Pb]VMT-α-NET Targeted Alpha-Particle Therapy
for Advanced SSTR2 Positive Neuroendocrine Tumors
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
[212Pb]VMT-α-NET
Description:
Patients with positive uptake on FDA approved SSTR2 PET/CT will receive a fixed dose of
[212Pb]VMT-α-NET IV administered every 8 weeks for a maximum of four doses
Arm group label:
Dose Escalation
Intervention type:
Drug
Intervention name:
[212Pb]VMT-α-NET
Description:
Patients with positive uptake on FDA approved SSTR2 PET/CT will receive a fixed dose of
[212Pb]VMT-α-NET IV administered at the RPh2D and schedule determined in Phase I dose
escalation
Arm group label:
Dose Expansion with RPh2D
Summary:
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
Detailed description:
This is a prospective, multi-center open-label dose escalation, dose expansion study of
[212Pb]VMT-α-NET in up to 160 adult subjects with unresectable or metastatic
SSTR2-expressing neuroendocrine tumors (NETs) who have not received prior peptide
receptor radionuclide therapy (PRRT).
The radioactivity dose escalation period (Phase I) tests up to 4 escalating radioactivity
dose cohorts of up to 8 subjects (administered at approximately 8-week intervals) at the
assigned cohort radioactivity dose.
Pre-specified dose adjustments and individual stopping rules for repeat treatment cycles
are based on observed dose-limiting toxicities (DLTs) and adverse events (AEs).
Additionally, up to 40 subjects may be enrolled in each of the cohorts.
The Maximum Tolerated Dose (MTD) will be determined based on observed DLTs within 42 days
of the first treatment cycle.
The recommended expansion (Phase IIa) dose(s) will be determined following a holistic
analysis of observed DLTs, AEs, estimated cumulative organ radiation exposure, and
efficacy signals over the course of all treatment cycles for all dose cohorts.
If MTD can not be identified within the 4 radioactivity dose cohorts, a Maximum Feasible
Dose (MFD), incorporating manufacturing and logistical considerations for
[212Pb]VMT-α-NET production, may be determined.
Up to 120 subjects will be considered for enrollment in the dose-expansion phase (Phase
IIa) with approximately 100 subjects with GEP-NETs, approximately 10 subjects with
bronchial NETs [small cell lung cancer], and approximately 10 subjects with
pheochromocytoma or paragangliomas)
Reno-protective amino acids will be co-administered in a separate IV line prior to each
[212Pb]VMT-α-NET dose in all subjects. Escalation will be based on a modified toxicity
probability interval design [mTPI-2] until MTD is identified or the pre-specified rules
are met.
A lead-in dosimetry sub-study will be conducted during the dose escalation period in
which all subjects in the first two dose cohorts will undergo dosimetric evaluation prior
to receiving the therapeutic agent.
Criteria for eligibility:
Criteria:
Inclusion 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.
Exclusion Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
90 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic
Address:
City:
Jacksonville
Zip:
32224
Country:
United States
Status:
Recruiting
Contact:
Phone:
904-953-2000
Email:
CANCERCTR@mayo.edu
Investigator:
Last name:
Jason Starr, MD
Email:
Principal Investigator
Facility:
Name:
Biogenix Molecular
Address:
City:
Miami
Zip:
33165
Country:
United States
Status:
Recruiting
Contact:
Last name:
Milka Vina
Phone:
786-791-1799
Email:
mvina@cira-health.com
Investigator:
Last name:
Frankis Almaguel, MD
Email:
Principal Investigator
Facility:
Name:
The University of Chicago
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Contact:
Phone:
773-702-1000
Email:
cancerclinicaltrials@bsd.uchicago.edu
Investigator:
Last name:
Chih-Yi Liao, MD
Email:
Principal Investigator
Facility:
Name:
University of Iowa
Address:
City:
Iowa City
Zip:
52242
Country:
United States
Status:
Recruiting
Contact:
Phone:
319-356-1616
Email:
yusuf-menda@uiowa.edu
Contact backup:
Phone:
(319) 356-3214
Investigator:
Last name:
Yusuf Menda, MD
Email:
Principal Investigator
Facility:
Name:
University of Kentucky
Address:
City:
Lexington
Zip:
40536
Country:
United States
Status:
Recruiting
Contact:
Last name:
Yvonne Taul
Phone:
859-323-2354
Email:
yvonne.taul@uky.edu
Investigator:
Last name:
Lowell Anthony, MD, FACP
Email:
Principal Investigator
Facility:
Name:
Johns Hopkins
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Status:
Recruiting
Contact:
Phone:
410-955-6785
Email:
lsolnes1@jhmi.edu
Investigator:
Last name:
Lilja Solnes, MD
Email:
Principal Investigator
Facility:
Name:
BAMF Health
Address:
City:
Grand Rapids
Zip:
49503
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ilhana Vila
Phone:
616-729-0288
Email:
Ilhana.vila@bamfhealth.com
Investigator:
Last name:
Brandon Mancini, MD
Email:
Principal Investigator
Facility:
Name:
Michigan Health Professionals
Address:
City:
Troy
Zip:
48098
Country:
United States
Status:
Recruiting
Contact:
Last name:
Samuel Ceckowski
Phone:
313-461-9281
Email:
Samuel.ceckowski@profoundresearch.io
Investigator:
Last name:
Savitha Balaraman, MD
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Neda Tehrani
Phone:
507-538-5714
Email:
tehrani.neda@mayo.edu
Investigator:
Last name:
Thorvardur R Halfdanarson, MD
Email:
Principal Investigator
Facility:
Name:
Washington University
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
John Crandall
Phone:
314-747-5561
Email:
jcrandall@wustl.edu
Investigator:
Last name:
Richard Wahl, MD
Email:
Principal Investigator
Facility:
Name:
Nebraska Cancer Specialists
Address:
City:
Omaha
Zip:
68130
Country:
United States
Status:
Recruiting
Contact:
Last name:
Scott Degenhardt, NMAA
Phone:
402-691-5257
Email:
sdegenhardt@nebraskacancer.com
Investigator:
Last name:
Samuel Mehr, MD
Email:
Principal Investigator
Facility:
Name:
Virginia Cancer Specialists
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Contact:
Last name:
Carrie Friedman
Phone:
703-280-5390
Email:
carrie.friedman@usoncology.com
Investigator:
Last name:
Gregory Sibley, MD
Email:
Principal Investigator
Start date:
September 27, 2023
Completion date:
December 26, 2029
Lead sponsor:
Agency:
Perspective Therapeutics
Agency class:
Industry
Source:
Perspective Therapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05636618
