211At-MABG in Adults With Advanced Neuroendocrine Cancers

Обзор

Phase I dose escalation study of 211At-MABG in adults with advanced pheochromocytoma / paraganglioma (PPGL) or other NET-overexpressing cancers (as evidenced by positive MIBG imaging) who are refractory to, lacking, or ineligible for approved treatments. Phase 1 dose-escalation will follow a standard 3+3 design with an expansion cohort at the recommended phase two dose (RP2D).

Вмешательства

• Препарат 1 MBq/k of 211At-MABG Fractionated
  Astatine-211 \[211At\] is a short-lived α emitter conjugated onto meta-astatobenzylguanidine (\[211At\]MABG)
• Препарат 2 MBq/k1 of 211At-MABG Fractionated
  Astatine-211 \[211At\] is a short-lived α emitter conjugated onto meta-astatobenzylguanidine (\[211At\]MABG)
• Препарат 4 MBq/k of 211At-MABG Fractionated
  Astatine-211 \[211At\] is a short-lived α emitter conjugated onto meta-astatobenzylguanidine (\[211At\]MABG)

Первичные конечные точки

• Evaluate overall study feasibility [Срок оценки: 4 weeks]
• Evaluate study feasibility overall study feasibility assessed for operational issues versus treatment-related adverse events. [Срок оценки: 4 weeks]

Вторичные конечные точки (10)

• Safety of fractionated dosing of 211At-MABG in adults with advanced (PPGL) or other NET-overexpressing cancers per patient level [Срок оценки: 4 weeks]
• Safety of fractionated dosing of 211At-MABG in adults with advanced (PPGL) or other NET-overexpressing cancers per 'dose level'. [Срок оценки: 4 weeks]
• The maximum tolerated dose (MTD) and/or Recommended Phase II Dose (RP2D) of 211At-MABG [Срок оценки: 8 weeks]
• Incidence of Adverse Events [Срок оценки: 72 months]
• The objective response rate (ORR) per RECIST 1.1 following a single cycle of fractionated dosing of 211At-MABG [Срок оценки: 72 months]
• The duration of response (DOR) following a single cycle of fractionated dosing of 211At-MABG [Срок оценки: 12 months]
• The Disease Control Rate (DCR) following a single cycle of fractionated dosing of 211At-MABG [Срок оценки: 12 months]
• Biochemical Response (BCR) [Срок оценки: 12 months]
• Anti-Hypertensive Medication Response [Срок оценки: 12 months]
• The time to subsequent anti-cancer therapy (time to next treatment) (TTNT) [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Adult patients, at least 18 years of age
• Advanced neuroendocrine cancers requiring systemic therapy and refractory to, ineligible for, declining, or lacking standard treatments.
• I MIBG imaging indicating MIBG-avid disease (radiotracer uptake above background in at least one tumor site) per Investigator/Sub-Investigator assessment.
• Participants must provide written informed consent prior to study-specific procedures.
• ECOG performance status ≤ 2.
• Adequate organ function including:

• Hemoglobin ≥ 9 g/dL
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 75,000/mm³
• Measured or estimated GFR ≥ 60 mL/min
• Serum bilirubin ≤ 1.5x upper limit of normal
• ALT/AST each ≤ 2.5x upper limit of normal
• Life expectancy at least 3 months as judged by treating physician

Критерии исключения

• Women who are pregnant or breast-feeding will not be eligible for this study.
• Inability to tolerate study procedures in the opinion of the investigator or treating physician.
• Serious or unstable medical, psychological, or social conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study.
• Uncontrolled brain metastasis (Participant must be at least 4 weeks since CNS-directed therapy and no longer requiring corticosteroid therapy).
• Anticancer therapy, except hormonal therapy or bone supportive therapies, within 14 days of cycle 1 day 1.
• Has a known additional malignancy (other than the disease under study) that has required active systemic treatment within the past 2 years AND for which the natural history or recent/ongoing treatment could likely interfere with study endpoints or safety of the study treatment per Investigator and Medical Director assessment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Pennsylvania - Abramson Cancer Center — Philadelphia

Идентификаторы

NCT: NCT07661420 · 26-6403 · 1R01CA300202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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