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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.

Publication ,  Journal Article
Grudzinski, JJ; Titz, B; Kozak, K; Clarke, W; Allen, E; Trembath, L; Stabin, M; Marshall, J; Cho, SY; Wong, TZ; Mortimer, J; Weichert, JP
Published in: PLoS One
2014

INTRODUCTION: (131)I-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 (131)I-CLR1404. METHODS: Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of (131)I-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 (127)I-CLR1404 mass measurements. To evaluate renal clearance of (131)I-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 (131)I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma (127)I-CLR1404 concentrations declined in a bi-exponential manner with a mean t½ value of 822 hours. Mean Cmax and AUC(0-t) values were 72.2 ng/mL and 15753 ng • hr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow. CONCLUSIONS: Preliminary data suggest that (131)I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent. TRIAL REGISTRATION: ClinicalTrials.gov NCT00925275.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

11

Start / End Page

e111652

Location

United States

Related Subject Headings

  • Whole Body Imaging
  • Tomography, X-Ray Computed
  • Tomography, Emission-Computed, Single-Photon
  • Tissue Distribution
  • Radiometry
  • Phospholipid Ethers
  • Neoplasms
  • Neoplasm Staging
  • Neoplasm Recurrence, Local
  • Neoplasm Metastasis
 

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Grudzinski, J. J., Titz, B., Kozak, K., Clarke, W., Allen, E., Trembath, L., … Weichert, J. P. (2014). A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety. PLoS One, 9(11), e111652. https://doi.org/10.1371/journal.pone.0111652
Grudzinski, Joseph J., Benjamin Titz, Kevin Kozak, William Clarke, Ernest Allen, LisaAnn Trembath, Michael Stabin, et al. “A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety.PLoS One 9, no. 11 (2014): e111652. https://doi.org/10.1371/journal.pone.0111652.
Grudzinski, Joseph J., et al. “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, 2014, p. e111652. Pubmed, doi:10.1371/journal.pone.0111652.
Grudzinski JJ, Titz B, Kozak K, Clarke W, Allen E, Trembath L, Stabin M, Marshall J, Cho SY, Wong TZ, Mortimer J, Weichert JP. A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety. PLoS One. 2014;9(11):e111652.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

11

Start / End Page

e111652

Location

United States

Related Subject Headings

  • Whole Body Imaging
  • Tomography, X-Ray Computed
  • Tomography, Emission-Computed, Single-Photon
  • Tissue Distribution
  • Radiometry
  • Phospholipid Ethers
  • Neoplasms
  • Neoplasm Staging
  • Neoplasm Recurrence, Local
  • Neoplasm Metastasis