Head and Neck Squamous Cell CarcinomaPhase 2NCT03953976
INRT-AIR: A Prospective Phase II Study of Involved Nodal Radiation Therapy
A Phase 2 study testing Intensity modulated radiation therapy (IMRT) in people with Head and Neck Squamous Cell Carcinoma, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
Elective nodal irradiation has been a longstanding standard-of-care in the management of mucosal squamous cell carcinoma of the head and neck. Recent studies have suggested that reduced elective dose and volume may be a viable approach to improve toxicity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Intensity modulated radiation therapy (IMRT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jul 2019to 22 Jan 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx, larynx, or hypopharynx. Squamous cell carcinoma of unknown primary is not allowed.
- Patients must have clinically or radiographically evident measureable disease at the primary site and/or nodal stations. Diagnostic lymph node excision (< 2 nodes) is also allowable.
- Patients may undergo a diagnostic or therapeutic transoral resection for a T1-2 tonsil or base of tongue cancer.
- Clinical stage I-IVB (AJCC, 7th edition); stages I-II glottic cancer are excluded
- Age ≥ 18 years.
- ECOG Performance Status 0-2
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- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- 7.1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Negative serum pregnancy test within 2 weeks before registration for women of childbearing potential.
- Neck CT and/or neck MRI, and PET-CT (at least skull-to-thigh).
- Ability to understand and the willingness to sign a written informed consent.
Who cannot join
- Distant metastasis.
- Inability to undergo PET-CT.
- Stage I and II glottic carcinoma.
- Gross total excision of both the primary and nodal disease.
- Synchronous non-skin cancer primaries outside of the oropharynx, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer; in the latter case, surgery may occur before or after treatment, provided all other eligibility criteria are met .
- Prior invasive malignancy with an expected disease-free interval of less than 3 years.
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- Prior systemic chemotherapy for the study cancer; prior chemotherapy for a remote cancer is allowable
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields.
- Subjects may not be receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study (if necessary).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements
- Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
- History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, 75390
About this study
Official title: INRT- AIR: A Prospective Phase II Study of Involved Nodal Radiation Therapy Using Artificial Intelligence-Based Radiomics for Head and Neck Squamous Cell Carcinoma
Elective nodal irradiation has been a longstanding standard-of-care in the management of mucosal squamous cell carcinoma of the head and neck. Recent studies have suggested that reduced elective dose and volume may be a viable approach to improve toxicity. In this study, we are eliminating the elective neck treatment, focusing therapy on involved and suspicious nodes.
Read the detailed description
We recently completed and reported a successful study (INFIELD) using reduced elective dose (40 Gy) and volume (involved echelons + 1) for oropharynx and larynx cancer. In INRT-AIR (Involved Nodal Radiotherapy using AI-based Radiomics), we are eliminating the elective neck treatment altogether, using radiologic and radiomic-based criteria to focus treatment on the nodes themselves. Eligible patients include previously untreated patients with stage I-IVB oropharynx, larynx and hypopharynx cancer, excluding T1-2 glottic carcinoma. Patients requiring chemotherapy may receive cisplatin, cetuximab, or carboplatin-paclitexel.
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- Intensity modulated radiation therapy (IMRT)
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intensity modulated radiation therapy (IMRT)Radiation
Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel). 6.5-7 weeks of radiotherapy or chemoradiotherapy
| Study group | Role | What they receive |
|---|---|---|
| PET-CT at 3 months and ENT evaluation | Experimental | Treatment to the gross primary and nodal disease (70 Gy), with suspicious nodes treated to 66.5 Gy, all in 35 fractions. CT and PET-CT are required for nodal assessment. Restaging PET-CT must be performed between 11-14 weeks from the completion of treatment. The patient must see an otolaryngologist after the PET-CT to decide on post-treatment neck dissection per the surgeon's judgement. Patients will then be seen every 3 months (+/- 2 weeks) for the first year, and then at least every 6 months (+/-2 weeks) until the 36 month. Subsequent and intervening follow-up visits will be made per physician preference Receives: Radiation: Intensity modulated radiation therapy (IMRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Risk of Solitary Elective Volume Recurrence Following Elective Volume Reduction Using INRT
Definition: solitary means that the recurrence occurred without a preceding or synchronous in-field or distant recurrence By definition, local recurrence (LR) means disease recurrence in the primary site, and regional recurrence (RR) is a nodal failure anywhere in the neck. Patients who experienced either an LR or RR (or both), were also coded as a locoregional recurrence.
Measured: 2 years
Secondary outcomes (9)
Comparison of SEVR Risks by Anatomic Site
OS= Overall survival PFS= Progression-free survival
Measured: 2 years
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Summary Score and Functional Subscales
The EORTC QLQ-C30 is a 30-item instrument (30 questions). Results are calculated from the means of the scores from the summary score and the functional QLQ-C30 scales. Higher scores indicate better quality of life, on a scale from 0 to 100.
Patients answer questions that are grouped into the following scales:
Summary score (scored from 0-100, with higher scores indicating a better quality of life)
-Global (Patients rate overall health and quality of life)
Functional scales (each of these is scored from 0-100, with higher scores indicating a better quality of life)
- Physical function (ability to perform physical tasks)
- Role function (ability to perform daily and work-related activities)
- Emotional function (whether patient is experiencing distress, anxiety, depression)
- Cognitive function (memory, concentration)
- Social function (ability to maintain social activities and relationships)
Measured: Baseline, 3 months, 6 months, 12 months, 24 months
European Organization for Research and Treatment of Cancer Head and Neck 35-question Questionnaire (EORTC HN35) Symptom Subscales
Patients report to which extent they experience symptoms or problems during one week.
EORTC HN35 subscales are each scored on a scale from 0 to 100, with higher scores indicating worse symptoms. These subscales include dry mouth, sticky saliva, senses (taste/smell), pain, and speech issues
Measured: Baseline, 3 month, 6 month, 12 month, 24 months
MD Anderson Dysphagia Inventory (MDADI) Global, Emotional, Functional and Physical Subscales
Questionnaire asks for patients' views about swallowing ability. MDADI scores range from 20 to 100, where higher scores represent better swallowing ability.
Measured: Baseline, 3 months, 6 months, 12 months, 24 months
Skin Toxicity (Dermatitis)
According to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v4.0 toxicity criteria Higher grades indicate worse adverse events. This is assessed clinically by the patient's physician.
Grade 1 is defined as "Faint erythema or dry desquamation" Grade 2 is defined as "Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin folds and creases; moderate edema" Grade 3 is defined as "Moist Desquamation in areas other than skin folds and creases; bleeding induced by minor trauma or abrasion"
Measured: 2 years
Gastrostomy Placement
Number of patients who experienced gastrostomy dependence for a period of time following treatment with INRT up to 2 years post treatment
Measured: from end of treatment to 2 years post treatment
EQ-5D Quality of Life Overall Health Visual Analogue Scale (VAS)
Average patient utilities (derived from EQ-5D) at baseline, 1, 3, 6, 12, 18, 24 and 36 months from the end of treatment. The overall health VAS is scored from 0 (worst imaginable health) to 100 (best imaginable health) based on the patient's self-reported health that day.
Measured: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months from the end of treatment
2-year Overall and Progression-free Survival Following Treatment With INRT
Overall survival (PFS) is defined as the duration of time from start of treatment to time of progression (LR, RR, or DM) or death.
Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression (LR, RR, or DM) or death.
Measured: 2 years
Time From the End of Treatment for Disease-free Patients to Have Their Gastrostomy Tubes Removed
Median length of gastrostomy dependence following treatment with INRT for patients who had needed a gastrostomy tube inserted and who were deemed disease-free
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2019
- Study start23 Jul 2019
- Primary completion15 Nov 2022
- Study completion22 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Sher, University of Texas Southwestern Medical Center
- Investigators
- David J Sher, MD, MPH, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03953976
- Sponsor's protocol ID
- STU 2019-0711
- Status last verified
- Oct 2025
- First submitted
- 13 May 2019
- Last updated
- 19 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INRT- AIR: A Prospective Phase II Study of Involved Nodal Radiation Therapy Using Artificial Intelligence-Based Radiomics for Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT03953976
- Acronym / sponsor ID
- STU 2019-0711
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 23 Jul 2019 (actual)
- Primary completion
- 15 Nov 2022 (actual)
- Study completion
- 22 Jan 2024 (actual)
- First posted
- 17 May 2019 (actual)
- Results
- Posted 19 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Elective nodal irradiation has been a longstanding standard-of-care in the management of mucosal squamous cell carcinoma of the head and neck. Recent studies have suggested that reduced elective dose and volume may be a viable approach to improve toxicity. In this study, we are eliminating the elective neck treatment, focusing therapy on involved and suspicious nodes.
Detailed description
We recently completed and reported a successful study (INFIELD) using reduced elective dose (40 Gy) and volume (involved echelons + 1) for oropharynx and larynx cancer. In INRT-AIR (Involved Nodal Radiotherapy using AI-based Radiomics), we are eliminating the elective neck treatment altogether, using radiologic and radiomic-based criteria to focus treatment on the nodes themselves. Eligible patients include previously untreated patients with stage I-IVB oropharynx, larynx and hypopharynx cancer, excluding T1-2 glottic carcinoma. Patients requiring chemotherapy may receive cisplatin, cetuximab, or carboplatin-paclitexel.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PET-CT at 3 months and ENT evaluation | Experimental | Radiation: Intensity modulated radiation therapy (IMRT)Treatment to the gross primary and nodal disease (70 Gy), with suspicious nodes treated to 66.5 Gy, all in 35 fractions. CT and PET-CT are required for nodal assessment. Restaging PET-CT must be performed between 11-14 weeks from the completion of treatment. The patient must see an otolaryngologist after the PET-CT to decide on post-treatment neck dissection per the surgeon's judgement. Patients will then be seen every 3 months (+/- 2 weeks) for the first year, and then at least every 6 months (+/-2 weeks) until the 36 month. Subsequent and intervening follow-up visits will be made per physician preference |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx, larynx, or hypopharynx. Squamous cell carcinoma of unknown primary is not allowed.
- Patients must have clinically or radiographically evident measureable disease at the primary site and/or nodal stations. Diagnostic lymph node excision (< 2 nodes) is also allowable.
- Patients may undergo a diagnostic or therapeutic transoral resection for a T1-2 tonsil or base of tongue cancer.
- Clinical stage I-IVB (AJCC, 7th edition); stages I-II glottic cancer are excluded
- Age ≥ 18 years.
Key exclusion criteria (13 listed)
- Distant metastasis.
- Inability to undergo PET-CT.
- Stage I and II glottic carcinoma.
- Gross total excision of both the primary and nodal disease.
- Synchronous non-skin cancer primaries outside of the oropharynx, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer; in the latter case, surgery may occur before or after treatment, provided all other eligibility criteria are met .
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intensity modulated radiation therapy (IMRT)Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel). 6.5-7 weeks of radiotherapy or chemoradiotherapy | Radiation | PET-CT at 3 months and ENT evaluation |
Primary outcome
Risk of Solitary Elective Volume Recurrence Following Elective Volume Reduction Using INRT
Time frame: 2 years
Definition: solitary means that the recurrence occurred without a preceding or synchronous in-field or distant recurrence By definition, local recurrence (LR) means disease recurrence in the primary site, and regional recurrence (RR) is a nodal failure anywhere in the neck. Patients who experienced either an LR or RR (or both), were also coded as a locoregional recurrence.
9 secondary outcomes
Comparison of SEVR Risks by Anatomic Site
Time frame: 2 years
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Summary Score and Functional Subscales
Time frame: Baseline, 3 months, 6 months, 12 months, 24 months
European Organization for Research and Treatment of Cancer Head and Neck 35-question Questionnaire (EORTC HN35) Symptom Subscales
Time frame: Baseline, 3 month, 6 month, 12 month, 24 months
MD Anderson Dysphagia Inventory (MDADI) Global, Emotional, Functional and Physical Subscales
Time frame: Baseline, 3 months, 6 months, 12 months, 24 months
Skin Toxicity (Dermatitis)
Time frame: 2 years
Gastrostomy Placement
Time frame: from end of treatment to 2 years post treatment
EQ-5D Quality of Life Overall Health Visual Analogue Scale (VAS)
Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months from the end of treatment
2-year Overall and Progression-free Survival Following Treatment With INRT
Time frame: 2 years
Time From the End of Treatment for Disease-free Patients to Have Their Gastrostomy Tubes Removed
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David J Sher, MD, MPH principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intensity modulated radiation therapy (IMRT) in people with Head and Neck Squamous Cell Carcinoma, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Risk of Solitary Elective Volume Recurrence Following Elective Volume Reduction Using INRT (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2026.