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Hypofractionated Adjuvant Radiotherapy for Resected Head and Neck Cancers (HART-HN)

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ClinicalTrials.gov Identifier: NCT05120947
Recruitment Status : Recruiting
First Posted : November 16, 2021
Last Update Posted : January 11, 2022
Sponsor:
Information provided by (Responsible Party):
Musaddiq Awan, Medical College of Wisconsin

Brief Summary:
The primary purpose of this study is to determine the safe reduction of the treatment fractions to 10, 8, or 5, that may be delivered safely in resected head and neck squamous cell carcinoma (HNSCC) patients with intermediate pathologic risk features.

Condition or disease Intervention/treatment Phase
Resectable Head and Neck Squamous Cell Carcinoma Radiation: 42 Gy Radiation Therapy Radiation: 39 Gy Radiation Therapy Radiation: 32.5 Gy Radiation Therapy Not Applicable

Detailed Description:
RATIONALE: Postoperative hypofractionated radiation is well established in many malignancies, yielding benefits in compliance, access to care, convenience, and cost savings. In several solid tumor types, short-course high dose-per-fraction (hypofractionated) post-operative radiation has shown excellent tolerability, reduced healthcare costs, improved compliance, and at least equivalent cancer control compared to conventional post-operative radiation (long course, low dose-per-fraction).(1-3) Despite advances in other malignancies, hypofractionated post-operative radiation is not used in previously untreated mucosal HNSCCs, for which an extended course of conventional post-operative radiation (usually 60 Gy in 2 Gy fractions delivered over six weeks) remains the standard. Hypofractionation has been stymied in the post-operative setting for HNSCCs primarily due to concerns of toxicity in treating a large mucosal field and an inability to spare critical structures such as the brain and spinal cord. These concerns were well-founded in the 1970s during the era of 2-dimensional radiotherapy when conventional HNSCC radiotherapy regimens were developed.(4) But because radiotherapy can be delivered far more precisely using intensity modulated radiation therapy (IMRT), it is hypothesized that post-operative radiation for HNSCCs can now be delivered safely in only five fractions delivered over one week.(3, 5, 6)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This study will use a time-to-event continual reassessment method (TITE-CRM) for assigning subjects to the radiation therapy dosages.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Hypofractionated Adjuvant Radiotherapy for Resected Head and Neck Cancers (HART-HN)
Actual Study Start Date : December 1, 2021
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : January 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 42 Gray (Gy) Radiation
42 gy of radiation therapy will be administered in 10 fractions.
Radiation: 42 Gy Radiation Therapy
Radiation Therapy: Dose per fraction of 4.2 Gy.

Experimental: 39 Gray (Gy) Radiation
39 gy of radiation therapy will be administered in 8 fractions.
Radiation: 39 Gy Radiation Therapy
Radiation Therapy: Dose per fraction of 4.875 Gy.

Experimental: 32.5 Gray (Gy) Radiation
32.5 gy of radiation therapy will be administered in 5 fractions.
Radiation: 32.5 Gy Radiation Therapy
Radiation Therapy: Dose per fraction of 6.5 Gy.




Primary Outcome Measures :
  1. Maximum-tolerated Radiation Dose [ Time Frame: 12 months ]
    This will be determined as the radiation dose with the minimum number of fractions at which there is no more than a 33% rate of dose-limiting toxicity (DLT) up to 12 months after completion of radiation treatment using the TITE-CRM design.

  2. Incidence of Dose-Limiting Toxicities [ Time Frame: 12 months ]
    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 :
  1. Overall Survival [ Time Frame: One year ]
    This measure is the number of subjects alive at one year following the conclusion of scheduled radiation therapy.

  2. Locoregional progression [ Time Frame: One year ]
    This measure is the number of subjects showing disease progression in the head and neck by response evaluation criteria in solid tumors (RECIST) criteria.

  3. MD Anderson Dysphagia Inventory Global Score [ Time Frame: Baseline, up to 2 weeks during radiotherapy, weeks 2, 4 and 6 following radiation therapy; months 3, 6, 9 and 12 following radiation therapy. ]
    This measure comprises a single five-item, Likert-style question with responses ranging from 'Strongly Agree' to 'Strongly Disagree'. A higher score ('Strongly Agree') corresponds to a worse outcome.

  4. MD Anderson Dysphagia Inventory Composite Score [ Time Frame: Baseline, up to 2 weeks during radiotherapy, weeks 2, 4 and 6 following radiation therapy; months 3, 6, 9 and 12 following radiation therapy. ]
    This measure comprises 19 five-item, Likert-style questions with responses ranging from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that higher scores ('Strongly Agree') corresponds to worse traits or more severe symptoms.

  5. MD Anderson Dysphagia Inventory Score (Emotional) [ Time Frame: Baseline, up to 2 weeks during radiotherapy, weeks 2, 4 and 6 following radiation therapy; months 3, 6, 9 and 12 following radiation therapy. ]
    This measure is the score for the "emotional" domain comprising a subset of five-item, Likert-style questions of the MD Anderson Dysphagia Inventory Composite tool that assesses symptoms relevant to emotional health. Responses range from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that higher scores ('Strongly Agree') correspond to worse traits or more severe symptoms.

  6. MD Anderson Dysphagia Inventory Score (Functional) [ Time Frame: Baseline, up to 2 weeks during radiotherapy, weeks 2, 4 and 6 following radiation therapy; months 3, 6, 9 and 12 following radiation therapy. ]
    This measure is the score for the "functional" domain comprising a subset of five-item, Likert-style questions of the MD Anderson Dysphagia Inventory Composite tool that assesses symptoms relevant to the ability to function in daily life activities. Responses range from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that higher scores ('Strongly Agree') correspond to worse traits or more severe symptoms.

  7. MD Anderson Dysphagia Inventory Score (Physical) [ Time Frame: Baseline, up to 2 weeks during radiotherapy, weeks 2, 4 and 6 following radiation therapy; months 3, 6, 9 and 12 following radiation therapy. ]
    This measure is the score for the "physical" domain comprising a subset of five-item, Likert-style questions of the MD Anderson Dysphagia Inventory Composite tool that assesses symptoms relevant to the ability to perform physical activities. Responses range from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that higher scores ('Strongly Agree') correspond to worse traits or more severe symptoms.

  8. Functional Assessment of Cancer Therapies- Head and Neck (FACT-HN) [ Time Frame: Baseline, up to 2 weeks during radiotherapy, weeks 2, 4 and 6 following radiation therapy; months 3, 6, 9 and 12 following radiation therapy. ]
    Quality of life scale with 4 sub-scales and 12 items each related specifically to head and neck cancer quality of life. The Physical Health scale has 7 items, each rated 0-4. Scores range from 0-28 with a lower score indicating better quality of life. The Social Well Being scale has 7 items, each rated 0-4. Scores range from 0-28 with a higher score indicating better quality of life. The Emotional Well Being scale has 6 items, each rated 0-4. Scores range from 0-24 with a lower score indicating better quality of life. The Functional scale has 7 items, each rated 0-4. Scores range from 0-28 with a higher score indicating better quality of life. The remaining 12 items are all scored as 0-4 each, range for each item 0-4 with higher or lower score indicating better quality life depending on each individual item.

  9. Functional Assessment of Cancer Therapies- Head and Neck (Physical Well-being) [ Time Frame: Baseline, up to 2 weeks during radiotherapy, weeks 2, 4 and 6 following radiation therapy; months 3, 6, 9 and 12 following radiation therapy. ]
    The Physical Well-being scale has seven items, each rated 0-4. Scores range from 0-28 with a lower score indicating better quality of life.

  10. Functional Assessment of Cancer Therapies- Head and Neck (Social/Family Well-being) [ Time Frame: Baseline, up to 2 weeks during radiotherapy, weeks 2, 4 and 6 following radiation therapy; months 3, 6, 9 and 12 following radiation therapy. ]
    The Social Well-being scale has seven items, each rated 0-4. Scores range from 0-28 with a higher score indicating better quality of life.

  11. Functional Assessment of Cancer Therapies- Head and Neck (Emotional Well-being) [ Time Frame: Baseline, up to 2 weeks during radiotherapy, weeks 2, 4 and 6 following radiation therapy; months 3, 6, 9 and 12 following radiation therapy. ]
    The Emotional Well-being scale has 6 items, each rated 0-4. Scores range from 0-24 with a lower score indicating better quality of life.

  12. Functional Assessment of Cancer Therapies- Head and Neck (Functional Well-being) [ Time Frame: Baseline, up to 2 weeks during radiotherapy, weeks 2, 4 and 6 following radiation therapy; months 3, 6, 9 and 12 following radiation therapy. ]
    The Functional Well-being scale has 7 items, each rated 0-4. Scores range from 0-28 with a higher score indicating better quality of life.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients 18 years or older with gross totally resected (R0 resection) Human papillomavirus (HPV) -negative squamous cell carcinoma of the head and neck (squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, nasal cavity, paranasal sinuses or carcinoma of unknown head/neck primary) who have at least 1 of the following intermediate risk factors for adjuvant radiation:

    1. Pathologic Node Positive Disease
    2. Perineural Invasion
    3. Oral cavity cancer with depth of invasion of at least 5 mm
    4. Lymphovascular Space Invasion
    5. Pathologic T3 or T4 disease
  2. Zubrod performance status 0-2.
  3. Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up.
  4. Inclusion of Covid-19 positive patients will be based on standard institutional protocol.
  5. Female patients must meet one of the following:

    • Postmenopausal for at least one year before the screening visit, or
    • Surgically sterile (i.e. undergone a hysterectomy or bilateral oophorectomy), or
    • If subject is of childbearing potential (defined as not satisfying either of the above two criteria), agree to practice two acceptable methods of contraception (combination methods requires use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive) from the time of signing of the informed consent form through 90 days after the last dose of study agent, AND o Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptom-thermal, post ovulation methods] and withdrawal are not acceptable contraception methods).
  6. Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:

    • Practice effective barrier contraception during the entire study period and through 60 calendar days after the last dose of study agent, OR
    • Must also adhere to the guidelines of any study-specific pregnancy prevention program, if applicable, OR o Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptom-thermal, post ovulation methods] and withdrawal are not acceptable methods of contraception.)
  7. Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion Criteria:

  1. Pathologic evidence of extranodal extension.
  2. Pathologic evidence of a final positive margin (R1 resection) or gross residual disease (R2 resection).
  3. HPV-positive squamous cell carcinoma.
  4. Prior invasive malignancy within the past 3 years (except for non-melanomatous skin cancer, and early stage treated prostate cancer).
  5. Life expectancy less than 12 months.
  6. Performance status Zubrod ≥ 3.
  7. Patients with prior radiation therapy to the head and neck Note: Prior external beam radiotherapy is excluded, but Iodine 131 is allowed.
  8. Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer.
  9. Body weight ≤ 30 kg.
  10. 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.
  11. Unstable angina and/or congestive heart failure requiring hospitalization within 3 months prior to Step 1 registration.
  12. Transmural myocardial infarction within three months prior to Step 1 registration.
  13. Medical or psychiatric illness which would compromise the patient's ability to tolerate treatment or limit compliance with study requirements.
  14. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during treatment and for 6 months after radiation, this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. Women who are breastfeeding are also excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05120947


Contacts
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Contact: Medical College of Wisconsin Cancer Center Clinical Trials Office 414-805-8900 cccto@mcw.edu
Contact: Igli Arapi 414-805-4365 iarapi@mcw.edu

Locations
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United States, Wisconsin
Froedtert & the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Igli Arapi    414-805-4365    iarapi@mcw.edu   
Sponsors and Collaborators
Medical College of Wisconsin
Investigators
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Principal Investigator: Musaddiq Awan, MD Medical College of Wisconsin
Publications:

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Responsible Party: Musaddiq Awan, Assistant Professor, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT05120947    
Other Study ID Numbers: PRO00042119
First Posted: November 16, 2021    Key Record Dates
Last Update Posted: January 11, 2022
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Musaddiq Awan, Medical College of Wisconsin:
Head and Neck Squamous Cell Carcinoma
Hypofraction Adjuvant Radiation
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site