sEphB4-HSA With Cetuximab and RT in Patients With High Risk, LAHNSCC and Heavy Smoking Histories
Summary
This is a Phase I dose-escalation study of sEphB4-HSA in combination with 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.
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 Design
Conditions
High Risk, Locally-advanced Squamous Cell Carcinoma of Head and Neck
Intervention
sEphB4-HSA with cetuximab and radiation
Status
Not yet recruiting
Source
University of Colorado, Denver
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT04091867
- ClinicalTrials.gov processed this data on September 20, 2019
Published on BioPortfolio: 2019-09-23T04:51:50-0400
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Medical and Biotech [MESH] Definitions
Pregnancy, High-risk
Pregnancy in which the mother and/or FETUS are at greater than normal risk of MORBIDITY or MORTALITY. Causes include inadequate PRENATAL CARE, previous obstetrical history (ABORTION, SPONTANEOUS), pre-existing maternal disease, pregnancy-induced disease (GESTATIONAL HYPERTENSION), and MULTIPLE PREGNANCY, as well as advanced maternal age above 35.
Risk Reduction Behavior
Reduction of high-risk choices and adoption of low-risk quantity and frequency alternatives.
Technology, High-cost
Advanced technology that is costly, requires highly skilled personnel, and is unique in its particular application. Includes innovative, specialized medical/surgical procedures as well as advanced diagnostic and therapeutic equipment.
Radiation, Ionizing
Electromagnetic or corpuscular radiation capable of producing ions, directly or indirectly, in its passage through matter. The wavelengths are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays and high-energy elementary particles.
Cosmic Radiation
High-energy radiation or particles from extraterrestrial space that strike the earth, its atmosphere, or spacecraft and may create secondary radiation as a result of collisions with the atmosphere or spacecraft.
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