Bronchial Carcinoid, Gastroenteropancreatic Neuroendocrine Neoplasm, Medullary Thyroid Cancer, Neuroendocrine Tumors, Paraganglioma, Pheochromocytoma
Conditions
Brief summary
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).
Interventions
DRUG2 MBq/k1 of 211At-MABG Fractionated
Astatine-211 \[211At\] is a short-lived α emitter conjugated onto meta-astatobenzylguanidine (\[211At\]MABG)
DRUG4 MBq/k of 211At-MABG Fractionated
Astatine-211 \[211At\] is a short-lived α emitter conjugated onto meta-astatobenzylguanidine (\[211At\]MABG)
DRUG1 MBq/k of 211At-MABG Fractionated
Astatine-211 \[211At\] is a short-lived α emitter conjugated onto meta-astatobenzylguanidine (\[211At\]MABG)
Sponsors
University of Pennsylvania
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult patients, at least 18 years of age 2. Advanced neuroendocrine cancers requiring systemic therapy and refractory to, ineligible for, declining, or lacking standard treatments. 3. I MIBG imaging indicating MIBG-avid disease (radiotracer uptake above background in at least one tumor site) per Investigator/Sub-Investigator assessment. 4. Participants must provide written informed consent prior to study-specific procedures. 5. ECOG performance status ≤ 2. 6. Adequate organ function including: 1. Hemoglobin ≥ 9 g/dL 2. Absolute neutrophil count ≥ 1,500/mm³ 3. Platelet count ≥ 75,000/mm³ 4. Measured or estimated GFR ≥ 60 mL/min 5. Serum bilirubin ≤ 1.5x upper limit of normal 6. ALT/AST each ≤ 2.5x upper limit of normal 7. Life expectancy at least 3 months as judged by treating physician
Exclusion criteria
1. Women who are pregnant or breast-feeding will not be eligible for this study. 2. Inability to tolerate study procedures in the opinion of the investigator or treating physician. 3. 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. 4. Uncontrolled brain metastasis (Participant must be at least 4 weeks since CNS-directed therapy and no longer requiring corticosteroid therapy). 5. Anticancer therapy, except hormonal therapy or bone supportive therapies, within 14 days of cycle 1 day 1. 6. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate overall study feasibility | 4 weeks | Proportion of intended 211At-MABG fractionated doses that are successfully administered within the protocol-defined window (at the overall study level). |
| Evaluate study feasibility overall study feasibility assessed for operational issues versus treatment-related adverse events. | 4 weeks | Proportion of fractionated dose administrations either delayed and/or omitted due to operational issues (i.e. insufficient/delayed synthesis) versus treatment-related adverse events (at the overall study level). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of fractionated dosing of 211At-MABG in adults with advanced (PPGL) or other NET-overexpressing cancers per patient level | 4 weeks | The proportion of intended 211At-MABG fractionated doses that are successfully administered within the protocol-defined window assessed at the 'per patient level'. |
| Safety of fractionated dosing of 211At-MABG in adults with advanced (PPGL) or other NET-overexpressing cancers per 'dose level'. | 4 weeks | The proportion of intended 211At-MABG fractionated doses that are successfully administered within the protocol-defined window assessed at the 'per dose level' |
| The maximum tolerated dose (MTD) and/or Recommended Phase II Dose (RP2D) of 211At-MABG | 8 weeks | Highest dose level at which 0 or 1 DLT occurs in 6 DLT-evaluable subjects |
| Incidence of Adverse Events | 72 months | Type, frequency, severity, and attribution of adverse events. as assessed by CTCAE version 6.0 |
| The objective response rate (ORR) per RECIST 1.1 following a single cycle of fractionated dosing of 211At-MABG | 72 months | Proportion of participants with Partial Response (PR) or Complete Response (CR) per RECIST v1.1 criteria |
| The duration of response (DOR) following a single cycle of fractionated dosing of 211At-MABG | 12 months | Time from treatment initiation until Progressive Disease (as per RECIST v1.1 criteria) among study participants with PR or CR following a single cycle of fractionated dosing of 211At-MABG |
| The Disease Control Rate (DCR) following a single cycle of fractionated dosing of 211At-MABG | 12 months | Proportion of participants with PR or CR or Stable Disease (SD) per RECIST v1.1 criteria following a single cycle of fractionated dosing of 211At-MABG. |
| Biochemical Response (BCR) | 12 months | Percent change from baseline in serum or urine metanephrines and catecholamines following a single cycle of fractionated dosing of 211At-MABG |
| Anti-Hypertensive Medication Response | 12 months | Change from baseline in anti-hypertensive medication dose following a single cycle of fractionated dosing of 211At-MABG |
| The time to subsequent anti-cancer therapy (time to next treatment) (TTNT) | 12 months | time from the first administration of fractionated dose of 211At-MABG until the first administration of subsequent anti-cancer therapy |
Countries
United States
Contacts
CONTACTAbramson Cancer Center
PRINCIPAL_INVESTIGATORVivek Narayan, MD, MS
University of Pennsylvania
Outcome results
None listed