Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 12:31 AM
Ignite Modification Date:
2025-12-25 @ 12:31 AM
NCT ID:
NCT04091867
Brief Summary:
This is a Phase I dose-escalation study of sEphB4-HSA in combination with chemotherapy, cetuximab and radiotherapy (RT). The purpose is to estimate the maximum tolerated dose (MTD) that can be administered concurrently with Cetuximab and radiation in patients with locally advanced, Stage III or IV A-B squamous cell carcinomas of the head or neck with a history of at least ten pack-years of smoking.
Detailed Description:
RT combined with the EGFR-targeted agent cetuximab represents a valuable alternative to platinum-based CRT and is FDA-approved for initial treatment of LAHNSCC, but outcomes remain unfavorable. Recently, EphB4 has emerged as another rational target. While minimally expressed in normal tissue, it is highly expressed in LAHNSCC and has been implicated in resistance to both EGFR-targeted therapy and to RT. Suppression of EphB4 in the preclinical setting has enhanced tumor death and enhanced radiosensitivity. The novel agent sEphB4-HSA is a fusion protein that binds the ligand for EphB4 and leads to inhibition of tumor proliferation and angiogenesis. It was well-tolerated as monotherapy in a phase I trial but has yet to be explored in combination with radiotherapy or EGFR-directed treatments. A combined modality approach adding sEphB4-HSA to standard-of-care RT plus cetuximab represents a rational, targeted approach for investigation in patients with high risk LAHNSS p16-negative or any patient with heavy smoking histories. Moreover, a short window period of sEphB4-HSA monotherapy between baseline biopsy and repeat biopsy prior to initiation of cetuximab with RT will both minimize potential treatment delay and allow for the identification of potential biomarkers of response to sEphB4-HSA. Finally, a third optional biopsy, to be done if feasible after initiation of cetuximab-radiation, will allow us to identify radiosensitization markers and potential markers for treatment de-escalation. MTD.
Study:
NCT04091867
Study Brief:
Protocol Section:
NCT04091867