# Project 2:  Therapeutic Combination of CLR1404 with External Beam Radiation in Head and Neck Cancer

> **NIH NIH P50** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $161,906

## Abstract

PROJECT SUMMARY
Radiation is a central modality for Head and Neck Cancer (HNC) treatment with approximately two-thirds of
patients receiving radiation in the definitive, adjuvant or palliative setting. Although significant technical
advances have been made in the delivery and dose shaping of radiation with 3D-conformal and intensity
modulated radiation therapy (IMRT), normal tissue toxicity remains dose limiting. In the current proposal, we
will test a promising new radiolabeled molecule (CLR1404) developed over the last decade at the University of
Wisconsin. CLR1404 is a radiolabeled phospholipid molecule with powerful potential as an imaging agent
(labeled with 124I) and as a therapy agent (labeled with 131I). CLR1404 shows potent uptake and retention in
HNC thereby providing tumor-selective internal delivery of radiation to complement external beam radiation in
the treatment of HNC. Our hypothesis is that CLR1404 will induce tumor response in HNC model systems, and
demonstrate a favorable tolerance and response profile in a Phase I clinical trial for recurrent HNC patients in
combination with external beam radiation. Our three specific aims are: 1) Examine uptake and retention of
CLR1404 across a panel of HNC xenografts in mouse models, 2) Quantify the ability of CLR1404 to augment
external beam radiation response in HNC xenograft model systems, and 3) Perform a Phase I clinical trial that
combines CLR1404 with reduced-dose external beam radiation in patients with locoregional recurrence
following prior HNC radiation. This trial will examine feasibility, toxicity, tumor response, salivary and
swallowing function, and HN-specific quality of life (QOL). We will highlight the use of 124I-CLR1404 using PET-
CT imaging as the ideal biomarker to guide the subsequent personalized therapy prescription with 131I-
CLR1404. This work is innovative and significant because it is the first study to examine combined external
beam radiation plus internal radiation with CLR1404 in patients with HNC. De-intensification of external beam
radiation dose, with reduction in normal tissue toxicities so common in HNC patients, supports the ultimate
objective to improve treatment outcome and QOL for HNC patients.

## Key facts

- **NIH application ID:** 9988233
- **Project number:** 5P50DE026787-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** PAUL M HARARI
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $161,906
- **Award type:** 5
- **Project period:** 2016-08-02 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988233

## Citation

> US National Institutes of Health, RePORTER application 9988233, Project 2:  Therapeutic Combination of CLR1404 with External Beam Radiation in Head and Neck Cancer (5P50DE026787-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9988233. Licensed CC0.

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