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

NCT05636618
clinicaltrials.gov
Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
300
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Lead sponsor
Perspective Therapeutics
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Start date
2023-09-27
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Number of sites
20
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Summary
This study is Phase I/IIa First-in-Human Study of \[212Pb\]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Tumors
clinicaltrials.gov
Short title
Targeted Alpha-Particle Therapy for Advanced Somatostatin Receptor Type 2 (SSTR2) Positive Tumors
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Official title
A Phase I/IIa First-in-Human Study of [212Pb]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Tumors
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2029-12-26
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First posted
2022-12-05
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Registry last updated
2026-10-13
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Primary completion date
2029-11-26
clinicaltrials.gov
Start date
2023-09-27
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Participants
300
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Participant count basis
Estimated
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Planned participants
300
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Protocol amendments
5
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Number of sites
20
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Perspective Therapeutics
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05636618
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ClinicalTrials.gov ID
NCT05636618
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Number of participants with dose-limiting toxicities (DLTs) after the first administration of [212Pb]VMT-α-NET

    Timeframe: Incidence and severity of DLTs during the first 42 days of study treatment will be assessed.

    DLTs describe side effects of a drug that are serious enough to prevent an increase in dose

  2. Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 in subjects with NETs

    Timeframe: Up to week 96

    Percentage of subjects with complete responses (CRs) or partial responses (PRs) to at least 1 administration of \[212Pb\]VMT-α-NET

  3. ORR per Response Assessment in Neuro-Oncology (RANO) meningioma criteria in subjects with meningioma

    Timeframe: Up to week 96

    Percentage of subjects with complete responses (CRs) or partial responses (PRs) to at least 1 administration of \[212Pb\]VMT-α-NET

  4. Number of subjects with adverse events (AEs)

    Timeframe: Until the end of study (3 years after end-of-study visit)

    Any untoward medical occurrence in a clinical investigational participant administered \[212Pb\]VMT-α-NET and which does not necessarily have a causal relationship with this treatment. Associated Adverse Events (AE) or Serious AEs are assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

  1. Anti-tumor efficacy of [212Pb]VMT-α-NET in terms of tumor response

    Timeframe: Until the end of study (3 years after end-of-study visit)

    Determination of the best overall response rate (BOR) by RECIST v1.1 in subjects with neuroendocrine tumors or RANO in meningioma subjects

  2. Determine the duration of response (DOR) receiving [212Pb]VMT-α-NET.

    Timeframe: Up to week 96

    The length of time that a tumor continues to respond to treatment without the cancer growing or spreading determined by RECIST v1.1 or RANO

  3. Determination of Progression-free survival (PFS)

    Timeframe: Up to week 96

    PFS is how long a subject lives without the disease worsening as evaluated by RECIST v1.1 or RANO

  4. To investigate the Overall Survival (OS) following treatment with [212Pb]VMT-α-NET

    Timeframe: Until the end of study (3 years after end-of-study visit)

    OS is how long a subject lives after a subject starts treatment

  5. Determination of pharmacokinetic properties of [212Pb]VMT-α-NET.

    Timeframe: 24 hours following [212Pb]VMT-α-NET dosing.

    Blood radioactivity pharmacokinetic parameter i.e. area under the plasma concentration versus time curve (AUC) is determined.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
90 Years
Healthy volunteers
No

  1. Adult (ages ≥18) PRRT-naïve subjects with NETs or meningioma by local pathology.
  2. Disease described clinically as: (a) Locally advanced/unresectable or metastatic NETs for dose-finding part of the study (b) Locally advanced/unresectable or metastatic GEP-NETs, bronchial NETs, pheochromocytoma, or paragangliomas for the dose-expansion part of the study (c) Requiring at least 1 prior surgery (resection/biopsy) and a maximum of 1 line of EBRT, if technically feasible, for meningioma.
  3. For meningioma: histologically confirmed diagnosis of meningioma, i.e., all grades (1 to 3) per World Health Organization Classification of Tumors of the Central Nervous System (5th edition; WHO-CNS5)
  4. Radiological evidence of measurable disease by: (a) For NETs: RECIST v1.1 criteria on CT with contrast or MRI of the areas of tumor involvement within 60 days of enrollment.
  5. Lesions must have shown radiological evidence of disease progression in the 12 months prior to enrollment. (b) For meningioma: RANO meningioma criteria on contrast-enhanced skull MRI for meningioma within 3 weeks prior to enrollment.
  6. Demonstration of lesional SSTR expression: (a) For NETs: using an FDA-approved somatostatin receptor PET imaging agent, e.g. [68Ga]DOTATATE, [64Cu]DOTATATE, or [68Ga]DOTATOC (b) For meningioma: using a standard-of-care SSTR PET imaging agent within 45 days of enrollment
  7. ECOG Performance Status ≤ 1.
  8. Subjects with HIV positivity are allowed if CD4 Count > 350 cells/μL.
  9. Concurrent Somatostatin Analog (SSA) Therapy use while on protocol therapy is allowed provided that 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
  10. For NETs: Progressive Disease on approved therapies other than radionuclide therapy.
  11. For subjects with meningioma who are receiving corticosteroid treatment, the dose must be ≤ 4 mg/day dexamethasone (or other corticosteroid equivalent dose) for a minimum of 7 days before the initiation of study treatment.
  12. Must have clinically demonstrated adequate catecholamine blockade if catecholamine-secreting pheochromocytoma/paraganglioma tumors are present.
  13. Able to understand and sign informed consent and comply with all study requirements.
  14. Life expectancy > 3 months.
  15. Satisfactory organ function as determined by laboratory testing.
  16. 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
  17. 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

  1. Known hypersensitivity to SSA, SSTR imaging agents or any of the excipients of [212Pb]VMT-α-NET.
  2. Known additional malignancy that is progressing or requires active treatment.
  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 (EBRT) must be completed at least 30 days prior to enrollment.
  9. Subjects who have received prior treatment with 90Y radioembolization or EBRT should have radiation absorbed dose to critical organs documented.
  10. Prior treatment with systemic anticancer therapy must be completed at least 30 days prior to enrollment (except for SSAs in subjects with functional tumors).
  11. Major surgery must be completed at least 30 days prior to enrollment.
  12. For Subjects with NETs: 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.
  13. Recently diagnosed and active infections requiring a time-limited course of antifungals or antibiotics in the 3 days prior to enrollment.
  14. Receipt of live attenuated vaccines in the 7 days prior to enrollment.
  15. 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
  16. Known medical condition which would make this protocol unreasonably hazardous for the subject.
  17. 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.
  18. Current abuse of alcohol or illicit drugs (exclusive of use of medically prescribed cannabinoids).
  19. 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.
  20. QTc > 450 milliseconds for males and females.
Sources for eligibility
clinicaltrials.gov

  • Mayo ClinicJacksonville, United StatesRecruiting
  • Biogenix MolecularMiami, United StatesRecruiting
  • Advent Health Radiation Oncology at Central FloridaOrlando, United StatesRecruiting
  • The University of ChicagoChicago, United StatesRecruiting
  • University of IowaIowa City, United StatesRecruiting
  • University of KentuckyLexington, United StatesRecruiting
  • Johns HopkinsBaltimore, United StatesRecruiting
  • Barbara Ann Karmanos Cancer InstituteDetroit, United StatesRecruiting
  • BAMF HealthGrand Rapids, United StatesRecruiting
  • Michigan Health ProfessionalsTroy, United StatesRecruiting
  • Mayo ClinicRochester, United StatesRecruiting
  • Washington UniversitySt Louis, United StatesRecruiting
  • Nebraska Cancer SpecialistsOmaha, United StatesRecruiting
  • University of North CarolinaChapel Hill, United StatesRecruiting
  • UH Cleveland Medical CenterCleveland, United StatesRecruiting
  • Ohio State UniversityColumbus, United StatesRecruiting
  • Vanderbilt-Ingram Cancer CenterNashville, United StatesRecruiting
  • Virginia Cancer SpecialistsFairfax, United StatesRecruiting
  • Fred Hutchinson Cancer CenterSeattle, United StatesRecruiting
  • Froedtert Medical College of WisconsinMilwaukee, United StatesRecruiting
Sources for sites
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (6)