Dose-Escalated Hypofractionated Adaptive Radiotherapy for Head and Neck Cancer

NCT04477759 | Completed Phase 1 Results DMC FDA Drug FDA Device

• 2 other identifiers: PRO00038841R21CA256144
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Head and Neck Neoplasm

Keywords

Radiotherapy; Atezolizumab; Targeted Radiation Therapy; Head and Neck Cancer; Cancer; Magnetic Resonance Guided Radiation Therapy

Outcome Measures

Primary Outcomes (5)

• Incidence of Dose-Limiting Toxicities at 50 Gy With Concurrent Atezolizumab

  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.

  12 months

• Incidence of Dose-Limiting Toxicities at 50 Gy

  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.

  12 months

• Incidence of Dose-Limiting Toxicities at 55 Gy

  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.

  12 months

• Incidence of Dose-Limiting Toxicities at 60 Gy

  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.

  12 months

• Maximum Tolerated Radiation Dose

  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.

  12 months

Secondary Outcomes (4)

• Overall Survival

  1 year

• Locoregional Progression

  1 year

• Gross Tumor Volume at Radiation Fraction 6 (Change From Baseline)

  6th Radiation Fraction (approximately 1 week)

• Gross Tumor Volume at Radiation Fraction 11 (Change From Baseline)

  11th Radiation Fraction (approximately 2 weeks)

Study Arms (4)

50 Gray (Gy) Radiation Therapy with Concurrent Atezolizumab

EXPERIMENTAL

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

Radiation: 50 Gy Radiation Therapy; Drug: Concurrent Atezolizumab

50 Gray (Gy) Radiation Therapy

EXPERIMENTAL

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

Radiation: 50 Gy Radiation Therapy; Drug: Adjuvant Atezolizumab

55 Gray (Gy) Radiation Therapy

EXPERIMENTAL

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

Radiation: 55 Gy Radiation Therapy; Drug: Adjuvant Atezolizumab

60 Gray (Gy) Radiation Therapy

EXPERIMENTAL

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

Radiation: 60 Gy Radiation Therapy; Drug: Adjuvant Atezolizumab

Interventions

50 Gy Radiation Therapy RADIATION

Ionizing radiation

50 Gray (Gy) Radiation Therapy; 50 Gray (Gy) Radiation Therapy with Concurrent Atezolizumab

55 Gy Radiation Therapy RADIATION

Ionizing radiation

55 Gray (Gy) Radiation Therapy

60 Gy Radiation Therapy RADIATION

Ionizing radiation

60 Gray (Gy) Radiation Therapy

Concurrent Atezolizumab DRUG

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.

Also known as: Tecentriq

50 Gray (Gy) Radiation Therapy with Concurrent Atezolizumab

Adjuvant Atezolizumab DRUG

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.

Also known as: Tecentriq

50 Gray (Gy) Radiation Therapy; 55 Gray (Gy) Radiation Therapy; 60 Gray (Gy) Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Diagnosis of T3-T4 N0-N3 M0 or T0-T4 N1-N3 M0 squamous cell carcinoma of the head and neck squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of unknown head/neck primary) based on American Joint Committee on Cancer guideline (AJCC; 8th edition) with measurable disease who meet at least 1 one of the following 3 criteria:
• \. Not a candidates for concurrent, bolus, cisplatin-based chemoradiation therapy based on one of the following criteria (a-e)
• Age ≥ 70 with moderate to severe comorbidity or vulnerability to cisplatin, defined as having one or more of the following conditions within 4 week of registration:
• Modified Charlson Comorbidity Index ≥ 1
• Adult Comorbidity Evaluation-27 (ACE-27) Index ≥ 1
• ω score \< 0.80
• Geriatric 8 (G-8) score ≤ 14
• Cancer and Aging Research Group (CARG) Toxicity Score ≥ 30%
• Cumulative Illness Rating Scale-Geriatric (CIRS-G) Score ≥ 4
• Age \< 70 with severe comorbidity or vulnerability to cisplatin, defined as having two or more of the following conditions within 4 weeks prior to registration:
• Modified Charlson Comorbidity Index ≥ 1
• ACE-27 Index ≥ 1
• ω score \< 0.80
• G-8 score ≤ 14

You may not qualify if:

• Prior invasive malignancy within the past 3 years (except for non-melanomatous skin cancer, and early stage treated prostate cancer);
• Life expectancy less than 12 months
• Performance status Zubrod \>3
• Inability to encompass all gross disease in 19 cm superior to inferior planning target volume to be treated on the MR LINAC
• MRI-incompatible foreign body
• Claustrophobia precluding ability to tolerate multiple MRIs
• MRI-incompatible pacemaker or implantable cardioverter defibrillator (ICD) placement
• Patients with Cochlear implant
• Patients with prior radiation therapy to the head and neck Note: Prior external beam radiotherapy is excluded, but Iodine 131 is allowed.
• Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer
• Major surgery within 28 days prior to registration
• Body weight ≤ 30 kg
• Any of the following severe laboratory abnormalities within 14 days of registration, unless corrected prior to it: Sodium \< 130 mmol/L or \> 155 mmol/L; Potassium \< 3.5 mmol/L or \> 6 mmol/L ;Fasting glucose \< 40 mg/dl or \> 400 mg/dl;Serum calcium (ionized or adjusted for albumin) \< 7 mg/dl or \> 12.5 mg/dl; Magnesium \< 0.9 mg/dl or \> 3 mg/dl
• Unstable angina and/or congestive heart failure requiring hospitalization within 3 months prior to Step 1 registration
• Transmural myocardial infarction within 3 months prior to Step 1 registration

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• National Cancer Institute (NCI): collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Neoplasms

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site

Results Point of Contact

• Title: Musaddiq Awan, MD
• Organization: Medical College of Wisconsin

mawan@mcw.edu

414-805-4497

Study Officials

• Musaddiq Awan, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

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

Study Record Dates

• First Submitted: July 15, 2020
• First Posted: July 20, 2020
• Study Start: January 26, 2021
• Primary Completion: April 8, 2024
• Study Completion: April 14, 2025
• Last Updated: July 15, 2025
• Results First Posted: July 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)