Head and Neck CancerPhase 2NCT06477692

Invert-Prospective Phase II Randomized Trial of Involved Nodal Versus Elective Neck RadioTherapy

A Phase 2 study testing ENI using IMRT with or without chemotherapy, INRT and ENI in people with Head and Neck Cancer, run by University of Texas Southwestern Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

To determine the risk of solitary elective volume recurrence following involved nodal radiotherapy (INRT) versus elective nodal irradiation (ENI) Read more about this study

Who is it for?: Ages 18 to 99 years
Conditions the study is for: Head and Neck Cancer
What is being tested?: ENI using IMRT with or without chemotherapy, INRT and ENI
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 80 participants
Where: 1 siteUnited States
Study dates: 14 Nov 2024to 1 Jul 2028
Phase: Phase 2
Are there results?: Not yet: the study is under way

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 to 99 years
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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All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, 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.
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).
Neck CT and/or neck MRI, and PET-CT
Ability to understand and the willingness to sign a written informed consent.

Who cannot join

Distant metastasis.
Inability to undergo either a diagnostic CT with contrast or simulation CT with contrast.
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.

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Prior invasive malignancy with an expected disease-free interval of less than 3 years.
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.
History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Sarah Neufeld contact

214-645-8525

Sarah.hardee@utsouthwestern.edu

Liliana Robles contact

214-645-8525

liliana.robles@utsouthwestern.edu

United States1 site, 1 recruiting

UT Southwestern Medical Center
Dallas, Texas, 75390
Sarah Neufeld, MS
David Sher, MD
Recruiting

Other trials in United States

About this study

Official title: INVERT - Prospective Phase II Randomized Trial of Involved Nodal Versus Elective Neck RadioTherapy

To determine the risk of solitary elective volume recurrence following involved nodal radiotherapy (INRT) versus elective nodal irradiation (ENI)

Read the detailed description

Patients are assigned to either elective nodal irradiation (ENI), the current treatment paradigm, or involved nodal radiotherapy (INRT), the experimental treatment. INRT is more specifically targeting potentially cancerous nodes, identified using an AI program developed in-house. The hope is that this more specific targeting will decrease healthy tissue being irradiated, therefore decreasing potential side effects of the radiation treatment.

Patients are blinded during study participation.

Conditions: Head and Neck Cancer
Being tested: ENI using IMRT with or without chemotherapy, INRT, ENI
Medical subject headings: Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ENI using IMRT with or without chemotherapyDrug
Also called cisplatin, cetuximab, or carboplatin- paclitaxel)
This study is a phase II single-blinded randomized trial comparing standard ENI with involved nodal radiotherapy. INRT using intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin- paclitaxel)
INRTRadiation
INRT using intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin- paclitaxel)
ENIRadiation
ENI using IMRT with or without chemotherapy

Study groups in NCT06477692
Study group	Role	What they receive
Standard radiotherapy with elective neck irradiation (ENI)	Active comparator	The elective neck dose is 56 Gy in 35 fractions Lymph nodes measuring 17 mm or greater in any dimension, or showing FDG above adjacent blood pool, may receive 63 Gy in 35 fractions per physician discretion.The elective neck field is determined by the primary site. The Oropharynx: Node-positive side: Levels IB-V and RP nodes Node-negative side: Levels II-IV, RP at discretion of physician For ipsilateral tonsil decision-making, see 4.1.1.6.3 The Larynx: Node-positive side: Levels IB-V Node-negative side: Levels II-IV Subglottic extension: Level VI Hypopharynx: Node-positive side: Levels IB-V and RP nodes Node-negative side: Levels II-V and RP nodes Pyriform sinus involvement: Level VI Receives: Drug: ENI using IMRT with or without chemotherapy; Radiation: ENI
Involved and suspicious lymph node delineation and targeting	Experimental	After the involved and suspicious nodes are contoured, the physician will contour remaining nodes that are present on more than one CT slice and submit them to the AI-Radiomics module for assessment.The nodal gross tumor volume (GTVn, GTVns and GTVnps for involved, suspicious nodes or potentially suspicious) will be contoured on the planning CT, using radiographic and clinical information to define its extent. The total dose for GTVns is 63 Gy in 35 fractions, and the total dose for GTVnps is 56 Gy in 35 fractions. For lymph nodes identified as potentially suspicious by the AI- Radiomics module that are outside of the expected primary draining zone, physicians may not treat the lymph node if the module assesses its estimation uncertainty as greater than 50%. Receives: Drug: ENI using IMRT with or without chemotherapy; Radiation: INRT

What is being measured

The primary outcome is the main question the study is designed to answer.

The probability at two years: SEVR in INRT versus ENI patients
The probability at two years will be compared between the arms using a one- sided Fisher's exact test (probability of SEVR between the arms).
Measured: 2 years

Secondary outcomes (3)

Incidence of Acute Grade 2+ Dermatitis between ENI vs INRT arms
Comparison of instances of grade 2+ acute dermatitis between patients treated with INRT (involved nodal radiotherapy, study treatment) vs ENI (elective nodal irradiation, standard of care). This will be compared between the arms using a Fisher exact test (2-sided).
Measured: Start of RT through 90 days post RT
Incidence of Grade 3+ Dysphagia between ENI vs INRT arms
Comparison of instances of grade 3+ dysphagia between patients treated with INRT (involved nodal radiotherapy, study treatment) vs ENI (elective nodal irradiation, standard of care). This will be compared between the arms using a Fisher exact test (2-sided).
Measured: 2 years post RT
MDADI Quality of Life composite score
Comparison of MDADI composite scores at 2 years post RT between patients treated with INRT (involved nodal radiotherapy, study treatment) vs ENI (elective nodal irradiation, standard of care). Patients with disease recurrence will be excluded from analysis. At two years, both scores will be compared between the arms using a two-sided T test.
Measured: 2 years post RT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Nov 20241 Jul 2028

First posted27 Jun 2024
Study start14 Nov 2024
Primary completion1 Jul 2028 (estimated)
Study completion1 Jul 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Head and Neck CancerStudies 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: Randomised
Intervention model: Parallel groups
Model description: radiation ENI versus INRT
Masking: Single blind
Who is masked: Participant
Enrolment: 80 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06477692
Sponsor's protocol ID: STU-2024-0603
Other IDs: 1R01CA251792-01A1
Status last verified: Apr 2026
First submitted: 21 Jun 2024
Last updated: 17 Apr 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: Yes
Individual data sharing: No

Publications

Young S, Moon DH, Wang J, Chen L, Lin MH, Zhu L, Ahn C, Hughes R, Sher DJ. Involved nodal versus elective neck radiotherapy (INVERT) for head and neck squamous cell carcinoma: a prospective phase II randomized controlled trial protocol. BMC Cancer. 2026 May 11;26(1):815. doi: 10.1186/s12885-026-15904-8.
PubMed 42116021

Study at a glance

From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: INVERT - Prospective Phase II Randomized Trial of Involved Nodal Versus Elective Neck RadioTherapy
ClinicalTrials.gov ID: NCT06477692
Acronym / sponsor ID: STU-2024-0603
Conditions: Head and Neck Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 80 participants (estimated)
Lead sponsor: University of Texas Southwestern Medical CenterUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 14 Nov 2024 (actual)
Primary completion: 1 Jul 2028 (estimated)
Study completion: 1 Jul 2028 (estimated)
First posted: 27 Jun 2024 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To determine the risk of solitary elective volume recurrence following involved nodal radiotherapy (INRT) versus elective nodal irradiation (ENI)

Detailed description

Patients are blinded during study participation.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 2
Model description: radiation ENI versus INRT

Arm	Type	Receives
Standard radiotherapy with elective neck irradiation (ENI)	Active comparator	Drug: ENI using IMRT with or without chemotherapy, Radiation: ENIThe elective neck dose is 56 Gy in 35 fractions Lymph nodes measuring 17 mm or greater in any dimension, or showing FDG above adjacent blood pool, may receive 63 Gy in 35 fractions per physician discretion.The elective neck field is determined by the primary site. The Oropharynx: Node-positive side: Levels IB-V and RP nodes Node-negative side: Levels II-IV, RP at discretion of physician For ipsilateral tonsil decision-making, see 4.1.1.6.3 The Larynx: Node-positive side: Levels IB-V Node-negative side: Levels II-IV Subglottic extension: Level VI Hypopharynx: Node-positive side: Levels IB-V and RP nodes Node-negative side: Levels II-V and RP nodes Pyriform sinus involvement: Level VI
Involved and suspicious lymph node delineation and targeting	Experimental	Drug: ENI using IMRT with or without chemotherapy, Radiation: INRTAfter the involved and suspicious nodes are contoured, the physician will contour remaining nodes that are present on more than one CT slice and submit them to the AI-Radiomics module for assessment.The nodal gross tumor volume (GTVn, GTVns and GTVnps for involved, suspicious nodes or potentially suspicious) will be contoured on the planning CT, using radiographic and clinical information to define its extent. The total dose for GTVns is 63 Gy in 35 fractions, and the total dose for GTVnps is 56 Gy in 35 fractions. For lymph nodes identified as potentially suspicious by the AI- Radiomics module that are outside of the expected primary draining zone, physicians may not treat the lymph node if the module assesses its estimation uncertainty as greater than 50%.

Who may qualify

Ages: 18 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 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 either a diagnostic CT with contrast or simulation CT with contrast.
Inability to undergo PET-CT.
Stage I and II glottic carcinoma.
Gross total excision of both the primary and nodal disease.

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
ENI using IMRT with or without chemotherapyAlso: cisplatin, cetuximab, or carboplatin- paclitaxel)This study is a phase II single-blinded randomized trial comparing standard ENI with involved nodal radiotherapy. INRT using intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin- paclitaxel)	Drug	Involved and suspicious lymph node delineation and targeting, Standard radiotherapy with elective neck irradiation (ENI)
INRTINRT using intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin- paclitaxel)	Radiation	Involved and suspicious lymph node delineation and targeting
ENIENI using IMRT with or without chemotherapy	Radiation	Standard radiotherapy with elective neck irradiation (ENI)

Primary outcome

The probability at two years: SEVR in INRT versus ENI patients
Time frame: 2 years
The probability at two years will be compared between the arms using a one- sided Fisher's exact test (probability of SEVR between the arms).

3 secondary outcomes

Incidence of Acute Grade 2+ Dermatitis between ENI vs INRT arms
Time frame: Start of RT through 90 days post RT
Incidence of Grade 3+ Dysphagia between ENI vs INRT arms
Time frame: 2 years post RT
MDADI Quality of Life composite score
Time frame: 2 years post RT

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
Derived from this study: PubMed 42116021Young S, Moon DH, Wang J, Chen L, Lin MH, Zhu L, Ahn C, Hughes R, Sher DJ. Involved nodal versus elective neck radiotherapy (INVERT) for head and neck squamous cell carcinoma: a prospective phase II randomized controlled trial protocol. BMC Cancer. 2026 May 11;26(1):815. doi: 10.1186/s12885-026-15904-8.
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.

Sarah Neufeld contact

214-645-8525

Sarah.hardee@utsouthwestern.edu

Liliana Robles contact

214-645-8525

liliana.robles@utsouthwestern.edu

David Sher, MD 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?

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 10 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: looking for participants now, as of the sponsor's last update on 17 Apr 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sarah Neufeld (214-645-8525, Sarah.hardee@utsouthwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The probability at two years: SEVR in INRT versus ENI patients (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06477692, which also lists 1 linked publication.

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 17 Apr 2026.