Abstract
Methods: Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of 131I-CLR1404. Whole body planar nuclear medicine scans were performed at 15-35 minutes, 4-6, 18-24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on 127I-CLR1404 mass measurements. To evaluate renal clearance of 131I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software.
Results: Single administrations of 370 MBq of 131I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma 127I-CLR1404 concentrations declined in a bi-exponential manner with a mean tK value of 822 hours. Mean Cmax and AUC(0-t) values were 72.2 ng/mL and 15753 ngNhr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow.
Conclusions: Preliminary data suggest that 131I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent.
Introduction: 131I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK) and safety profiles of 131I-CLR1404.
| Original language | English (US) |
|---|---|
| Article number | 0111652 |
| Journal | PLoS One |
| Volume | 9 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 17 2014 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors : Dosimetry, biodistribution, pharmacokinetics, and safety. / Grudzinski, Joseph J.; Titz, Benjamin; Kozak, Kevin; Clarke, William; Allen, Ernest; Trembath, Lisaann; Stabin, Michael; Marshall, John; Cho, Steve Y.; Wong, Terence Z.; Mortimer, Joanne; Weichert, Jamey P.
In: PLoS One, Vol. 9, No. 11, 0111652, 17.11.2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors
T2 - Dosimetry, biodistribution, pharmacokinetics, and safety
AU - Grudzinski, Joseph J.
AU - Titz, Benjamin
AU - Kozak, Kevin
AU - Clarke, William
AU - Allen, Ernest
AU - Trembath, Lisaann
AU - Stabin, Michael
AU - Marshall, John
AU - Cho, Steve Y.
AU - Wong, Terence Z.
AU - Mortimer, Joanne
AU - Weichert, Jamey P.
PY - 2014/11/17
Y1 - 2014/11/17
N2 - Methods: Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of 131I-CLR1404. Whole body planar nuclear medicine scans were performed at 15-35 minutes, 4-6, 18-24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on 127I-CLR1404 mass measurements. To evaluate renal clearance of 131I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software.Results: Single administrations of 370 MBq of 131I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma 127I-CLR1404 concentrations declined in a bi-exponential manner with a mean tK value of 822 hours. Mean Cmax and AUC(0-t) values were 72.2 ng/mL and 15753 ngNhr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow.Conclusions: Preliminary data suggest that 131I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent.Introduction: 131I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK) and safety profiles of 131I-CLR1404.
AB - Methods: Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of 131I-CLR1404. Whole body planar nuclear medicine scans were performed at 15-35 minutes, 4-6, 18-24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on 127I-CLR1404 mass measurements. To evaluate renal clearance of 131I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software.Results: Single administrations of 370 MBq of 131I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma 127I-CLR1404 concentrations declined in a bi-exponential manner with a mean tK value of 822 hours. Mean Cmax and AUC(0-t) values were 72.2 ng/mL and 15753 ngNhr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow.Conclusions: Preliminary data suggest that 131I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent.Introduction: 131I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK) and safety profiles of 131I-CLR1404.
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U2 - 10.1371/journal.pone.0111652
DO - 10.1371/journal.pone.0111652
M3 - Article
VL - 9
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 11
M1 - 0111652
ER -