A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors

Dosimetry, biodistribution, pharmacokinetics, and safety

Joseph J. Grudzinski, Benjamin Titz, Kevin Kozak, William Clarke, Ernest Allen, Lisaann Trembath, Michael Stabin, John Marshall, Steve Y. Cho, Terence Z. Wong, Joanne Mortimer, Jamey P. Weichert

Research output: Contribution to journalArticle

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 languageEnglish (US)
Article number0111652
JournalPLoS One
Volume9
Issue number11
DOIs
StatePublished - Nov 17 2014

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Pharmacokinetics
Refractory materials
pharmacokinetics
Dosimetry
Tumors
injection
Safety
neoplasms
Neoplasms
urine
renal clearance
absorbed dose
Injections
antineoplastic agents
radionuclides
computed tomography
bone marrow
medicine
Bone Marrow
Urine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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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 journalArticle

Grudzinski, JJ, Titz, B, Kozak, K, Clarke, W, Allen, E, Trembath, L, Stabin, M, Marshall, J, Cho, SY, Wong, TZ, Mortimer, J & Weichert, JP 2014, 'A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: Dosimetry, biodistribution, pharmacokinetics, and safety', PLoS One, vol. 9, no. 11, 0111652. https://doi.org/10.1371/journal.pone.0111652
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. / A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors : Dosimetry, biodistribution, pharmacokinetics, and safety. In: PLoS One. 2014 ; Vol. 9, No. 11.
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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.",
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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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