Neoplasms

All Conditions

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Immunomodulating Agents

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

50 Gy of ionizing radiation therapy will be administered in 15 fractions.

55 Gy of ionizing radiation therapy will be administered in 15 fractions.

60 Gy of ionizing radiation therapy will be administered in 15 fractions.

50 Gy Radiation Therapy

55 Gy Radiation Therapy

60 Gy Radiation Therapy

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.

Medical College of Wisconsin Clinical Trials Office

Musaddiq Awan, MD

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.

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.

This study will use a time-to-event continual reassessment method (TITE-CRM) for assigning subjects to the radiation therapy dosages.

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

This measure is the number of subjects experiencing a dose-limiting toxicity. A dose-limiting toxicity is defined as an inability to complete radiation treatment within 30 days of the start of radiotherapy that is not deemed to be related to disease progression; OR an unacceptable toxicity within one year of treatment (Grade 4+ toxicity) that is probably or definitely related to radiation treatment as determined by the treating physician or a death within one year of treatment that is probably or definitely related to treatment.

This measure is the highest radiation dose at which there is a 30% or more rate of dose-limiting toxicity up to 12 months after completion of radiation treatment using the TITE-CRM design.

This measure is the number of subjects alive at 1 year following the conclusion of scheduled radiation therapy.

This measure is the number of subjects showing disease progression in the head and neck by RECIST criteria.

This measure is the change in gross tumor volume for each subject as contoured on pre-treatment (baseline) and treatment 6 imaging scans. This will be measured in cubic centimeters.

This measure is the change in gross tumor volume for each subject as contoured on pre-treatment (baseline) and treatment 11 imaging scans. This will be measured in cubic centimeters.

Genentech, Inc.

National Cancer Institute (NCI)

Medical College of Wisconsin

Principal Investigator

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Musculoskeletal Diseases

Rare Diseases

Carcinoma

Paranasal Sinus Neoplasms

Nose Neoplasms

Otorhinolaryngologic Neoplasms

Nose Diseases

Respiratory Tract Diseases

Paranasal Sinus Diseases

Respiratory Tract Neoplasms

Otorhinolaryngologic Diseases

Sinus Cancer

Cisplatin

cisplatin

targeted radiation therapy

tumor resection

Sandeep Samant, MS, FRCS

The purpose of this study is to determine the efficacy of concurrent chemotherapy and radiotherapy pre-operatively in patients with advanced paranasal sinus cancer. The main objectives of this study are: 1) to measure the rate of complete response to preoperative chemoradiation and 2) to study the efficacy of combining preoperative chemoradiation and surgery in terms of local control of the cancer two years post treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Dose-Escalated Hypofractionated Adaptive Radiotherapy for Head and Neck Cancer	NCT04477759	Head and Neck N...	50 Gy Radiation... 55 Gy Radiation... 60 Gy Radiation... Atezolizumab	18 Years -	Medical College of Wisconsin
Chemoradiotherapy Followed by Surgery for Advanced Paranasal Sinus Cancer	NCT00347256	Paranasal Sinus...	cisplatin targeted radiat... tumor resection	18 Years -	University of Tennessee

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