NCT04091867

sEphB4-HSA With RT+Chemo or Cetux in Patients With Intermediate to High Risk LAHNSCC

A Phase I/Ib Study of sEphB4-HSA in Combination With Chemotherapy or Cetuximab and Radiation Therapy in Patients With Intermediate to High Risk, Locally-Advanced Squamous Cell Carcinomas of the Head and Neck

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: University of Colorado, Denver · Academic / Other
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Squamous Cell Carcinoma of Head and Neck

Interventions

Type	Name	Description
DRUG	sEphB4-HSA with chemotherapy	sEphB4-HSA is a fusion protein combining the soluble extracellular EphB4 domain with albumin that targets the ephrin B2 receptor, which is thought to mediate resistance to EGFR-targeted therapy, and acts as a radiosensitizer by enhancing DNA damage and promoting apoptosis. Concurrent chemotherapy drug (either cisplatin or carboplatin): Per treating physician discretion, and treatment plan is based per NCCN guidelines. These can be administered in tri-weekly or weekly doses during the radiation period. The participant will receive the first infusion on Day 15 (+/- 3 days).
DRUG	Cetuximab	Loading dose 400 mg/m2 on D9 Concurrent dose 250mg/m2 weekly D15± 3 day window
RADIATION	Radiation Therapy	6930 cGy IMRT starting D15-D18

Timeline

• Start date: 2020-01-06
• Primary completion: 2021-05-14
• Completion: 2022-10-25
• First posted: 2019-09-17
• Last updated: 2025-02-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study