AlphaMedix™ (²¹²Pb-DOTAMTATE) is a radiotherapeutic drug indicated in subjects with unresectable, metastatic somatostatin receptor (SSTR) positive neuroendocrine tumors (NETs). Because 212Pb is an in vivo generator of alpha particles, it is particularly suitable for SSTR therapy applications. This drug addresses an unmet need in the field of peptide receptor radionuclide therapy (PRRT) for NETs. Substitution of an alpha emitter (²¹²Pb) for the beta emitters currently being used (i.e., 177Lu or 90Y) will provide significantly higher Linear Energy Transfer (LET) and a shorter path length. Higher LET particles should cause more tumor cell death. Shorter path length should result in less collateral damage of the normal tissue and therefore less side effects for subjects receiving the drug.
This dose escalation study will include a maximum of 50 subjects with histologically confirmed NET, a positive somatostatin analogue scan, and no prior history of PRRT therapy. The study will begin with a single ascending dose (SAD) of AlphaMedix™ administered by IV. Subsequent cohorts will receive an incremental 30% increase that will continue until tumor response or DLT. Once tumor response is observed, the study will convert to a Multiple Ascending Dose (MAD) regimen. The MAD treatment regimen will start with the previous safe cohort's dose and will consist of 3 IV administrations of AlphaMedix™ at 8-week intervals. Subsequent cohorts will receive an incremental 30% increase that will continue until tumor response or DLT. The primary objective is to assess the safety and dose limiting toxicity (DLT) using ascending doses of AlphaMedix™. The secondary objectives are to determine the pharmacokinetic properties and preliminary effectiveness of AlphaMedix™.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
There is only a single treatment intervention.
Excel Diagnostics and Nuclear Oncology Center
Houston, Texas, United States
To determine dose-limiting toxicity (DLT)
DLT is defined as non-hematological toxicity - all Grade 4 and Grade 3 (except alk. phos.) that is not responsive to NMT 72 hours of supportive care - and all hematological toxicity that does not recover to NMT than Grade 2 within 8 wks of dose administration.
Time frame: 8 weeks post-injection
Incidence of treatment-emergent AEs and SAEs as assessed by CTCAE v. 4
AEs will be recorded both spontaneously by the patient during the treatment period and at all safety follow ups (2 wks, 4 wks, 6 wks, 8 wks post each injection and 3 mo, 6 mo, 10 mo, 12 mo, 15 mo, 18 mo, 21 mo, and 24 mo post last injection)
Time frame: 32 months after enrollment
Partial or complete response assessed by modified RECIST v1.1
CT/MRI or 18FDG-PET/CT (for patients who are FDG-avid at baseline) will be used to measure tumor size
Time frame: 32 months after enrollment
To determine effective blood clearance and cumulative blood activity of 212-Pb
Blood will be taken at Time 0, 1 hr, 4 hr and 24 hr post-injection and measured for activity in an auto gamma counter
Time frame: 24 hours post-injection
To determine the rate and extent of 212-Pb elimination in urine
Bladder will be emptied just prior to injection and qualitative urine collections will be done 0-1 hr, 1-4 hr and 4-24 hr post-injection and measured for activity in an auto gamma counter
Time frame: 24 hours post-injection
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