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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01CA300202 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Cancer Institute (NCI) | NIH |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Level -1: Fractionated 211At-MABG | Experimental | One treatment cycle (1 MBq/k) of 211At-MABG administered by IV administration in 4 fractionated (0.25 MBq/kg) weekly doses (+ 7 days) (one treatment cycle = 4 weekly fractionated doses). |
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| Dose Level 1: Fractionated 211At-MABG | Experimental | One treatment cycle (2 MBq/k) of 211At-MABG administered by IV administration in 4 fractionated (0.5 MBq/kg) weekly doses (+ 7 days) (one treatment cycle = 4 weekly fractionated doses). |
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| Dose Level 2: Fractionated 211At-MABG | Experimental | One treatment cycle (4 MBq/k) of 211At-MABG administered by IV administration in 4 fractionated (1 MBq/kg) weekly doses (+ 7 days) (one treatment cycle = 4 weekly fractionated doses). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 1 MBq/k of 211At-MABG Fractionated | Drug | Astatine-211 [211At] is a short-lived α emitter conjugated onto meta-astatobenzylguanidine ([211At]MABG) |
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| Measure | Description | Time Frame |
|---|---|---|
| Evaluate overall study feasibility | Proportion of intended 211At-MABG fractionated doses that are successfully administered within the protocol-defined window (at the overall study level). | 4 weeks |
| Evaluate study feasibility overall study feasibility assessed for operational issues versus treatment-related adverse events. | 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). | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Safety of fractionated dosing of 211At-MABG in adults with advanced (PPGL) or other NET-overexpressing cancers per patient level | The proportion of intended 211At-MABG fractionated doses that are successfully administered within the protocol-defined window assessed at the 'per patient level'. | 4 weeks |
| Safety of fractionated dosing of 211At-MABG in adults with advanced (PPGL) or other NET-overexpressing cancers per 'dose level'. |
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Inclusion Criteria:
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:
Life expectancy at least 3 months as judged by treating physician
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Abramson Cancer Center | Contact |
| Name | Affiliation | Role |
|---|---|---|
| Vivek Narayan, MD, MS | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania - Abramson Cancer Center | Philadelphia | Pennsylvania | 19104 | United States |
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| 2 MBq/k1 of 211At-MABG Fractionated | Drug | Astatine-211 [211At] is a short-lived α emitter conjugated onto meta-astatobenzylguanidine ([211At]MABG) |
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| 4 MBq/k of 211At-MABG Fractionated | Drug | Astatine-211 [211At] is a short-lived α emitter conjugated onto meta-astatobenzylguanidine ([211At]MABG) |
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The proportion of intended 211At-MABG fractionated doses that are successfully administered within the protocol-defined window assessed at the 'per dose level' |
| 4 weeks |
| The maximum tolerated dose (MTD) and/or Recommended Phase II Dose (RP2D) of 211At-MABG | Highest dose level at which 0 or 1 DLT occurs in 6 DLT-evaluable subjects | 8 weeks |
| Incidence of Adverse Events | Type, frequency, severity, and attribution of adverse events. as assessed by CTCAE version 6.0 | 72 months |
| The objective response rate (ORR) per RECIST 1.1 following a single cycle of fractionated dosing of 211At-MABG | Proportion of participants with Partial Response (PR) or Complete Response (CR) per RECIST v1.1 criteria | 72 months |
| The duration of response (DOR) following a single cycle of fractionated dosing of 211At-MABG | 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 | 12 months |
| The Disease Control Rate (DCR) following a single cycle of fractionated dosing of 211At-MABG | 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. | 12 months |
| Biochemical Response (BCR) | Percent change from baseline in serum or urine metanephrines and catecholamines following a single cycle of fractionated dosing of 211At-MABG | 12 months |
| Anti-Hypertensive Medication Response | Change from baseline in anti-hypertensive medication dose following a single cycle of fractionated dosing of 211At-MABG | 12 months |
| The time to subsequent anti-cancer therapy (time to next treatment) (TTNT) | time from the first administration of fractionated dose of 211At-MABG until the first administration of subsequent anti-cancer therapy | 12 months |
| ID | Term |
|---|---|
| D010673 | Pheochromocytoma |
| D010235 | Paraganglioma |
| D018358 | Neuroendocrine Tumors |
| D018276 | Carcinoma, Medullary |
| ID | Term |
|---|---|
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018278 | Carcinoma, Neuroendocrine |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D018299 | Neoplasms, Ductal, Lobular, and Medullary |
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