NCT04477759

Dose-Escalated Hypofractionated Adaptive Radiotherapy for Head and Neck Cancer

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: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Medical College of Wisconsin · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Head and Neck Neoplasm

Interventions

Type	Name	Description
RADIATION	50 Gy Radiation Therapy	Ionizing radiation
RADIATION	55 Gy Radiation Therapy	Ionizing radiation
RADIATION	60 Gy Radiation Therapy	Ionizing radiation
DRUG	Concurrent Atezolizumab	Atezolizumab (1,680 mg) will be given to all subjects by intravenous injection every 4 weeks following the initiation of radiation treatment up to 1 year from radiation fraction 1.
DRUG	Adjuvant Atezolizumab	Atezolizumab (1,680 mg) will be given to all subjects by intravenous injection every 28 days following the initiation of radiation treatment up to 1 year.

Timeline

• Start date: 2021-01-26
• Primary completion: 2024-04-08
• Completion: 2025-04-14
• First posted: 2020-07-20
• Last updated: 2025-07-15
• Results posted: 2025-07-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study