Dose-Escalated Hypofractionated Adaptive Radiotherapy for Head and Neck Cancer — DEHART  

Head and Neck Neoplasm Clinical Trial

Official title: A Phase I Trial of MR-Guided Dose-Escalated Hypofractionated Adaptive Radiation Therapy and Immunotherapy in Primary Metastatic or Very Locally Advanced Patients With Head and Neck Cancer

Status Recruiting

Clinical Trial Summary

Locoregional failure remains the principal mode of mortality in head and neck squamous cell carcinoma (HNSCC) treated with conventional chemoradiation therapy. Magnetic resonance-guided radiation therapy (MRgRT) allows for adaptive radiation dose escalation based on tumor response and may improve therapeutic outcomes while limiting toxicities.

This protocol evaluates a novel framework for radiation delivery with concurrent atezolizumab in patients with advanced HNSCC. Dose-Escalated Hypofractionated Adaptive Radiotherapy (DEHART) modifies radiation dose using MRgRT by escalating radiation dose to residual tumor while deescalating radiation dose to areas of tumor regression.

Clinical Trial Description

Locoregional failure remains the principal mode of mortality in head and neck squamous cell carcinoma (HNSCC) treated with conventional chemoradiation therapy. Radiation dose escalation with hypofractionation has shown unparalleled local control in other malignancies, such as non-small cell lung cancer, but has been limited in HNSCC due to toxicity concerns. Magnetic resonance-guided radiation therapy (MRgRT) allows for adaptive radiation dose escalation based on tumor response and may improve therapeutic outcomes while limiting toxicities.

This protocol evaluates a novel framework for radiation delivery using MRgRT with concurrent atezolizumab in patients with advanced HNSCC. Unlike conventional radiotherapy, Dose-Escalated Hypofractionated Adaptive Radiotherapy (DEHART) modifies radiation dose using MRgRT by adapting the radiation plan during the course of treatment, escalating radiation dose to residual tumor while deescalating radiation dose to areas of tumor regression. The hypothesis is that DEHART will safely deliver ablative radiation doses in 15 fractions over 3 weeks while limiting both toxicity and the effect of tumor repopulation by resistant clonogens, thus resulting in an improved therapeutic ratio.

This Phase I clinical trial will encompass the following specific aims: (1) determine the maximum tolerated dose (MTD) of the DEHART regimen delivered using MRgRT with concurrent atezolizumab in a population of patients who are not candidates or unsuitable for definitive chemoradiation therapy; (2) evaluate the toxicity and functional outcomes of the DEHART regimen; and (3) assess the efficacy of DEHART and obtain volumetric and functional imaging correlates of efficacy using MRgRT to serve as hypothesis-generating data for future trials of radiation dose adaptation. A modified Time-to Event Continual Reassessment (TITE-CRM) Phase I Design with three radiation dose levels delivered to regressing disease will be used to determine the MTD: 50 Gy in 15 fractions, 55 Gy in 15 fractions and 60 Gy in 15 fractions.

If DEHART is found to be safe and shows a signal of efficacy in this study, a future Phase II trial will be conducted to compare this novel treatment strategy to standard-of care conventionally fractionated chemoradiation in patients with locally advanced HNSCC. ;

Related Conditions & MeSH terms

• Head and Neck Neoplasm
• Head and Neck Neoplasms

• NCT number: NCT04477759
• Study type: Interventional
• Source: Medical College of Wisconsin
• Contact: Medical College of Wisconsin Clinical Trials Office
• Phone: 414-805-8900
• Email: cccto@mcw.edu
• Status: Recruiting
• Phase: Phase 1
• Start date: January 26, 2021
• Completion date: December 30, 2025