Postoperative Radiotherapy for Intermediate- and High-risk Patients With HNSCC Greater Than 6 Weeks After Surgery

July 10, 2026 updated by: Wake Forest University Health Sciences

A Randomized Trial of Accelerated Postoperative Radiotherapy for Intermediate- and High-risk Patients With HNSCC (Head and Neck Squamous Cell Carcinoma) Initiating Radiotherapy Greater Than 6 Weeks After Surgery (PORTRush)

The goal of this clinical trial is to determine whether accelerated radiotherapy (involving 6 treatments per week) is better than standard radiotherapy (involving 5 treatments per week) at treating cancer of the head and neck when initiated more than 6 weeks after surgery.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study is a randomized trial designed to determine the effect of Accelerated Fractionation (AF) versus Conventional Fractionation (CF) PORT on locoregional recurrence-free survival, progression-free survival, overall survival, toxicity, and treatment package time in participants with resected intermediate and high-risk Head and Neck Squamous Cell Carcinoma (HNSCC) planned to start Post Operative Radiotherapy (PORT) greater than six weeks after surgery. Eligible participants in both cohorts will be randomized 1:1 to receive five fractions per week of standard conventional fractionation radiotherapy or six fractions per week of accelerated fractionation radiotherapy. If randomized to the standard conventional fractionation group, participants will be treated with five fractions of radiation per week, received daily. If randomized to the accelerated fractionation group, participants will be treated with 6 fractions of radiotherapy per week, received daily and twice daily treatments on one day of the week.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
75

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest Baptist Comprehensive Cancer Center
        • Contact:
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • Recruiting
        • Advocate Aurora Radiation Oncology
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pathologically confirmed head and neck squamous cell carcinoma of the oral cavity, oropharynx, larynx, hypopharynx, sinus, or lymph nodes of the neck of unknown primary.

  • Planned for curative intent postoperative radiotherapy based on pathologic risk factors.

    • Patients with non-HPV-mediated oropharyngeal squamous cell carcinoma or non-oropharyngeal squamous cell carcinoma must have at least one of the following: pathologic tumor classification pT3-4, multiple lymph nodes involved with cancer, perineural invasion, lymphovascular invasion, close margins (within 2 mm for oropharyngeal cancer status post transoral resection; within 5 mm for all others) or cleared margins (initially positive, subsequently cleared in an additional specimen), extranodal extension (any extent), or positive surgical margins.
    • Patients with HPV-mediated oropharyngeal squamous cell carcinoma must have at least one of the following pathologic risk factors: extranodal extension (any extent), positive surgical margins, or more than 4 lymph nodes involved with cancer.
  • Complete macroscopic surgical resection with curative intent for HNSCC with an anticipated interval between the primary surgical resection and initiation of postoperative radiotherapy greater than 42 days but less than or equal to 112 days from surgery. Note: the start date of the time to initiation of PORT is the first (primary) surgical resection. This does not include diagnostic procedures (e.g., biopsy, diagnostic tonsillectomy) or any subsequent surgical interventions for any reason (e.g., wound complications).
  • Age ≥ 18 years at the time of enrollment.
  • ECOG performance status of 0-1.
  • Ability to understand and the willingness to sign an IRB-approved informed consent document directly, in English or Spanish, and to complete study-related forms and activities.

Exclusion Criteria:

  • Recurrent head and neck cancer that has recurred after prior courses of definitive RT or surgery followed by postoperative RT/CRT. Note that individuals who have been treated with surgery alone and are now recurrent are eligible.
  • Second primary head and neck cancer after initial treatment of a prior head and neck cancer.
  • History of prior radiotherapy to the head and neck region, such that any portion of the anticipated target volume overlaps with any region that was previously targeted.
  • Active malignancy other than the head and neck cancer to be treated with PORT (excluding non-melanoma skin cancer, in situ carcinoma of any site).
  • Metastatic disease from the head and neck cancer to be treated with PORT defined as distant organ involvement outside of the head and neck and/or non-regional lymph node involvement outside of the head and neck.
  • Time from primary surgical resection to anticipated initiation of PORT greater than 112 days.
  • 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 would limit compliance with study requirements
  • Not a candidate for radiation therapy per treating clinician. For example, individuals who are pregnant or plan to become pregnant (due to the risks of the developing fetus) or any other contraindication to radiation therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Conventional fractionation (5 Fractions)
5 fractions per week, daily treatment Monday-Friday; dosage at the discretion of the treating radiation oncologist per standard of care
Radiation: Conventional radiotherapy
5 fractions per week, daily M-F
Experimental: Accelerated fractionation (6 Fractions)
6 fractions per week, daily treatment plus twice daily treatment for 1 day Monday-Friday; dosage at the discretion of the treating radiation oncologist per standard of care
Radiation: Accelerated radiotherapy
6 fractions per week, BID fractions one day per week

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Locoregional Recurrence-free Survival
Time Frame: 2 years post radiotherapy
Time to locoregional recurrence, will be assessed on an intention to treat basis using a one-sided log rank test to compare hazard rates between groups. Kaplan-Meier survival curves will also be generated with locoregional failure or death as the event of interest and last clinical disease assessment as a right-censor.
2 years post radiotherapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS)
Time Frame: up to 5 years
Progression-free survival will be calculated from the time of randomization to disease recurrence or death from any cause as the event and last follow-up as a right-censor. It will be compared between treatment arms.
up to 5 years
Overall survival (OS)
Time Frame: up to 5 years
Overall survival will be calculated from the time of randomization to death from any cause, with last follow-up as a right-censor.
up to 5 years
Acute and late toxicities
Time Frame: up to 24 months post radiotherapy
Acute and late toxicities between each treatment arm will be measured by evaluating adverse events (AEs) by grade in each treatment arm. Using the Chi-square test (or Fisher's exact test if cell frequencies <5) and a significance level of 0.05, comparisons will be made of the following outcomes between treatment arms: 1) the number of participants with at least one AE of grade 3 or higher, 2) the number of participants with grade 1 or higher toxicity, and 3) the number of patients with grade 3 or higher toxicity. Each of these analyses will result in the construction of 2x2 tables thus the use of the Chi-Square (or Fisher's exact test) will be appropriate. These analyses will be completed for both acute (between RT start and 90 days after RT) and late (more than 90 days after RT completion) toxicities.
up to 24 months post radiotherapy
Patient Report Outcomes (PRO) - PRO-CTCAE
Time Frame: at baseline, end radiotherapy (RT), 3, 6, 12, and 24-months post RT
PRO-CTCAE measure of toxicity will be assessed by describing the counts and frequencies for the worst score observed in each participant in the whole cohort and by treatment arm. Using the Chi-square test (or Fisher's exact test if cell frequencies <5) and a significance level of 0.05, a comparison will occur of the following outcomes between treatment arms: 1) the number of patients with at least one PRO-CTCAE score of grade 1 or higher, and 2) the number of patients with at least one PRO-CTCAE score of grade 3 or higher. These comparisons 1 and 2 will be completed for both acute (between RT start and 90 days after RT) and late (more than 90 days after RT completion) toxicities. The analysis of change in PRO-CTCAE score over time will also be performed using a likelihood-based Generalized Linear Mixed Model (GLMM) approach.
at baseline, end radiotherapy (RT), 3, 6, 12, and 24-months post RT
Patient Reported Outcomes (PRO) - MDASI-HN
Time Frame: at End of Radiotherapy (RT), 3, 6, 12, and 24-months post RT
The MDASI-HN is a 28-item measure with three subscales: the 13 core MDASI items, 9 head and neck cancer-specific items, and 6 items specific to interference in daily life by the patient's symptoms. The change from baseline at each time point will be summarized using mean and standard deviation at end RT, 3, 6, 12, and 24-months post RT.
at End of Radiotherapy (RT), 3, 6, 12, and 24-months post RT
Nutritional Toxicity
Time Frame: up to 24 months post Radiotherapy
Nutritional toxicity will be measured by comparing the rates of reactive gastrostomy tube placement using a Fisher's exact test. For patients in whom a feeding tube is placed, the duration of tube will be defined as the time from tube placement to removal or last follow-up with a tube (right-censor) and will be estimated using the Kaplan-Meier method and compared between groups using the log-rank statistics.
up to 24 months post Radiotherapy
Time to initiation of Postoperative Radiotherapy (PORT)
Time Frame: up to 16 weeks
Time to initiation of PORT will be calculated as the number of days from date of primary curative resection (surgery date = day 0) to initiation of RT. This value will be compared between groups using a 2-sample t-test to see if there is a significant difference between groups on this covariate.
up to 16 weeks
Treatment package time
Time Frame: from surgical resection to end of PORT - up to approx. 165 days
The treatment package time will be calculated as the number of days from the primary surgical resection to the end of PORT (the last RT treatment for participants who complete therapy; for participants who do not complete the prescribed course of RT, this metric is moot) and compared between groups using a 2-sample T-test. The proportion of patients with treatment package time less than 100 days will be determined and compared between groups using the Chi-square test (or Fisher's exact test if cell frequencies <5).
from surgical resection to end of PORT - up to approx. 165 days
Demographic characteristics of eligible participants
Time Frame: Prior to Radiotherapy (Pre-screening and baseline)
The characteristics (age, gender assigned at birth, race, ethnicity) of potentially eligible participants will be described using count and frequency for categorical variables and mean (standard deviation) and median (range) for continuous variables. These factors will be compared between groups who do and do not enroll on study using the Chi-square tests for categorical and 2-sample t-tests for continuous measures. For participants who choose not to enroll, the reasons and rationale provided to support that decision will be described using count and frequency.
Prior to Radiotherapy (Pre-screening and baseline)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Wake Forest University Health Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ryan Hughes, MD, Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 21, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 18, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 23, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00119512
  • ONC-HN-2406 (Other Identifier: Atrium Health)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings