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.
Radiation therapy for HNC is commonly associated with normal tissue toxicities including dry mouth, difficulty swallowing and reduced QOL. This research will develop a new technique to reduce the dose of external beam radiation by incorporating a radiolabeled molecule, CLR1404 that delivers tumor-selective internal radiation. This approach holds promise to enhance outcome for HNC patients and improve long term QOL.
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