Clinical Trials /

Dose-Escalated Hypofractionated Adaptive Radiotherapy for Head and Neck Cancer

NCT04477759

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dose-Escalated Hypofractionated Adaptive Radiotherapy for Head and Neck Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: IIT-AWAN-DEHART Study
  • NCT ID: NCT04477759

Conditions

  • Head and Neck Neoplasm

Interventions

DrugSynonymsArms
AtezolizumabTecentriq50 Gray (Gy) Radiation Therapy

Purpose

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. We
      hypothesize 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. To determine the MTD of the DEHART regimen, we propose using a
      modified Time-to Event Continual Reassessment (TITE-CRM) Phase I Design with three radiation
      dose levels delivered to regressing disease: 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, we will conduct a
      future Phase II trial to compare this novel treatment strategy to standard-of care
      conventionally fractionated chemoradiation in patients with locally advanced HNSCC.
    

Trial Arms

NameTypeDescriptionInterventions
50 Gray (Gy) Radiation TherapyExperimental50 Gy of ionizing radiation therapy will be administered in 15 fractions.
  • Atezolizumab
55 Gray (Gy) Radiation TherapyExperimental55 Gy of ionizing radiation therapy will be administered in 15 fractions.
  • Atezolizumab
60 Gray (Gy) Radiation TherapyExperimental60 Gy of ionizing radiation therapy will be administered in 15 fractions.
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of primary or recurrent T3-T4, N(any), M0 or T1-T4, N1-N3, M0 squamous cell
             carcinoma of the head and neck

          -  Zubrod performance status 0-3

          -  Measurable primary and/or nodal tumor in the head and neck region at the time of
             radiotherapy

          -  Ability to tolerate multiple magnetic resonance imaging (MRI) sessions

        Exclusion Criteria:

          -  Prior radiation therapy to the head and neck

          -  History of autoimmune disease precluding ability to receive concurrent atezolizumab

          -  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

          -  Cochlear implant

          -  M0 subject who is a candidate for concurrent cisplatin-based chemoradiation therapy

          -  Metastatic squamous cell carcinoma of the head and neck
      
Maximum Eligible Age:N/A
Minimum Eligible Age:21 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Dose-Limiting Toxicities
Time Frame:12 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:1 year
Safety Issue:
Description:This measure is the number of subjects alive at 1 year following the conclusion of scheduled radiation therapy.
Measure:Locoregional progression
Time Frame:1 year
Safety Issue:
Description:This measure is the number of subjects showing disease progression in the head and neck by RECIST criteria.
Measure:Gross Tumor Volume at Radiation Fraction 6 (Change from Baseline)
Time Frame:6th Radiation Fraction (approximately 1 week)
Safety Issue:
Description:This measure is the change in gross tumor volume for each subject as contoured on pre-treatment (baseline) and treatment 6 imaging scans.
Measure:Gross Tumor Volume at Radiation Fraction 11 (Change from Baseline)
Time Frame:11th Radiation Fraction (approximately 2 weeks)
Safety Issue:
Description:This measure is the change in gross tumor volume for each subject as contoured on pre-treatment (baseline) and treatment 11 imaging scans.
Measure:MD Anderson Symptom Inventory for Head and Neck (MDASI-HN) Score
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:The MDASI-HN comprises 11-item Likert-style questions assessing 9 symptoms relevant to head and neck cancer. Responses range from 0 (no 'symptom') to 10 (severe 'symptom').
Measure:MDASI-HN Domain Score (Mucus in the Mouth and Throat)
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:This measure is the MDASI-HN score for the "mucus in the mouth and throat" domain.
Measure:MDASI-HN Domain Score (Difficulty Swallowing or Chewing)
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:This measure is the MDASI-HN score for the "difficulty swallowing or chewing" domain.
Measure:MDASI-HN Domain Score (Choking or Coughing)
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:This measure is the MDASI-HN score for the "choking or coughing" domain.
Measure:MDASI-HN Domain Score (Difficulty with Voice or Speech)
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:This measure is the MDASI-HN score for the "difficulty with voice or speech" domain.
Measure:MDASI-HN Domain Score (Skin Pain, Burning or Rash)
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:This measure is the MDASI-HN score for the "skin pain, burning or rash" domain.
Measure:MDASI-HN Domain Score (Constipation)
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:This measure is the MDASI-HN score for the "constipation" domain.
Measure:MDASI-HN Domain Score (Problems with Tasting Food)
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:This measure is the MDASI-HN score for the "problems with tasting food" domain.
Measure:MDASI-HN Domain Score (Mouth or Throat Sores)
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:This measure is the MDASI-HN score for the "mouth or throat sores" domain.
Measure:MDASI-HN Domain Score (Problems with Teeth or Gums)
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:This measure is the MDASI-HN score for the "problems with teeth or gums" domain.
Measure:MD Anderson Dysphagia Inventory (MDADI) Global Score
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:The MDADI global comprises a single five-item, Likert-style question with responses ranging from 'Strongly Agree' to 'Strongly Disagree'. 'Strongly Agree' response corresponds to a less desirable trait.
Measure:MD Anderson Dysphagia Inventory (MDADI) Composite Score
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:The MDADI survey comprises 19 five-item, Likert-style questions with responses ranging from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that 'Strongly Agree' responses correspond to less desirable traits or more severe symptoms.
Measure:MD Anderson Dysphagia Inventory (MDADI) Score (Emotional)
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:This measure is the subscore of the MDADI composite survey for the "emotional" domain.
Measure:MD Anderson Dysphagia Inventory (MDADI) Score (Functional)
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:This measure is the subscore of the MDADI composite survey for the "functional" domain.
Measure:MD Anderson Dysphagia Inventory (MDADI) Score (Physical)
Time Frame:Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1
Safety Issue:
Description:This measure is the subscore of the MDADI composite survey for the "physical" domain.
Measure:Eating Assessment Tool (EAT-10) Score
Time Frame:Baseline, and months 3 and 6 following fraction 1
Safety Issue:
Description:The Eating Assessment Tool comprises 10 five-item, Likert-style questions querying various aspects of swallowing. Responses range from 0 (No problem) to 4 (Severe problem). The total of the responses represents the EAT-10 score. Higher numbers indicate poorer swallowing ability.
Measure:Functional Oral Intake Scale (FOIS)
Time Frame:Baseline, and months 3 and 6 following fraction 1
Safety Issue:
Description:The Functional Oral Intake Scale is a clinician-completed ordinal rating scale ranging from 1 (No oral intake) to 7 (Total oral intake with no restrictions). Higher numbers indicate more favorable feeding capability.
Measure:Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) Grade
Time Frame:Baseline, and months 3 and 6 following fraction 1
Safety Issue:
Description:The DIGEST grade is a five-item modified barium swallow scale for grading pharyngeal dysphagia as a toxicity endpoint. The DIGEST grade responses are: grade 1= mild, grade 2= moderate, grade 3= severe, and grade 4= life threatening pharyngeal dysphagia.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Medical College of Wisconsin

Trial Keywords

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

Last Updated

July 15, 2020