Head and Neck CancerNCT05538533
Hypofractionated Preoperative Radiation for Head and Neck Cancers (HyPR-HN)
A study testing 46 Gy Radiation Therapy, 40 Gy Radiation Therapy and 35 Gy Radiation Therapy in people with Head and Neck Cancer, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
This is a phase 1 study to determine the safety of a condensed preoperative radiation regimen (10, 7, or 5 fractions) for the management of head and neck squamous cell carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- 46 Gy Radiation Therapy, 40 Gy Radiation Therapy and 35 Gy Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Jan 2023to 24 Aug 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Patients 18 years or older with surgically resectable, Human papillomavirus (HPV) -negative squamous cell carcinoma of the head and neck (squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, nasal cavity or paranasal sinuses). Resectability will be determined by the treating surgeon. Patients must have locoregionally advanced disease defined by clinical T3-4 staging and/or clinical node positive staging. Patients may also be eligible if they meet one of the following criteria:
- Clinical T2N0 disease with perineural invasion identified on a pretreatment biopsy.
- Clinical T2N0 disease with lymphovascular space invasion identified on a pretreatment biopsy.
- Clinical T2N0 oral cavity cancer with clinical, biopsy, or radiographic depth of invasion of at least 5 mm.
- Zubrod performance status 0-2.
- Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up.
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- Inclusion of COVID-19 positive patients will be based on standard institutional protocol.
- 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), agrees to practice two acceptable methods of contraception (combination methods require 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
- Agrees 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, postovulation methods] and withdrawal are not acceptable contraception methods).
- 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
- 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, postovulation methods] and withdrawal are not acceptable methods of contraception.
- Ability to understand a written informed consent document, and the willingness to sign it.
Who cannot join
- Radiographic evidence of extranodal extension.
- Patients with laryngeal involvement who are candidates for non-surgical laryngeal preservation as deemed by a surgeon and/or radiation oncologist. These patients include, but are not limited to, those with T1-T3 laryngeal cancer who do not have pretreatment tracheostomy and/or feeding tube or those with base of tongue/hypopharyngeal cancers with laryngeal involvement without cartilage invasion or pretreatment tracheostomy and/or feeding tube.
- HPV-positive squamous cell carcinoma.
- Prior invasive malignancy within the past three years (except for non-melanomatous skin cancer, and early stage treated prostate cancer).
- Life expectancy less than 12 months.
- Zubrod performance status ≥ 3.
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- Patients with prior radiation therapy to the head and neck (Note: Prior external beam radiotherapy is excluded, but iodine-131 is allowed).
- Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer.
- Body weight ≤ 30 kg.
- 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.
- Unstable angina and/or congestive heart failure requiring hospitalization within three months prior to step 1 registration.
- Transmural myocardial infarction within three months prior to step 1 registration.
- Medical or psychiatric illness which would compromise the patient's ability to tolerate treatment or limit compliance with study requirements.
- 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 six 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: A Phase I Study of Hypofractionated Preoperative Radiation for Head and Neck Cancers (HyPR-HN)
This is a phase 1 study to determine the safety of a condensed preoperative radiation regimen (10, 7, or 5 fractions) for the management of head and neck squamous cell carcinoma.
Read the detailed description
All subjects in this study will receive pre-operative hypofractionated radiation therapy, which will be subject to fractionation reduction, that being 10 fractions, 7 fractions, or 5 fractions, as compared to 30 fractions of conventional radiation therapy. All patients will subsequently undergo surgery for resection of remaining disease at the primary site and at-risk nodal basins 6-8 weeks after completion of radiation.
The subjects will receive smaller number of fractions (total visits) but with a higher dose of radiation with each Dose Level. Participants will receive a total radiation dose of 46 Gy in 10 fractions (Dose Level 1), 40 Gy in 7 fractions (Dose Level 2), or 35 Gy in 5 fractions (Dose Level 3), depending on the assigned experimental total fractions. Radiation will be delivered using intensity modulated radiation therapy (IMRT) with a daily cone-beam CT for five days a week, for less than two weeks depending on the assigned dose level at the time of enrollment.
Due to the novelty of translational data and non-dependency on the primary endpoint, presentation and publication in a scientific journal of the translational endpoints may precede publication of the primary endpoint.
- Conditions
- Head and Neck Cancer
- Being tested
- 46 Gy Radiation Therapy, 40 Gy Radiation Therapy, 35 Gy Radiation Therapy
- Keywords
- Head and Neck Cancer, Hypofractionated Preoperative Radiation, Time-to-Event Continuous Reassessment Methodology, TITE-CRM
- 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.
46 Gy Radiation TherapyRadiation
Dose per fraction of 4.6.
40 Gy Radiation TherapyRadiation
Dose per fraction 5.7.
35 Gy Radiation TherapyRadiation
Dose per fraction 7.0.
| Study group | Role | What they receive |
|---|---|---|
| 46 Gray (Gy) | Experimental | 46 gy of radiation therapy will be administered in 10 fractions. Receives: Radiation: 46 Gy Radiation Therapy |
| 40 Gray (Gy) | Experimental | 40 gy of radiation therapy will be administered in 7 fractions. Receives: Radiation: 40 Gy Radiation Therapy |
| 35 Gray (Gy) | Experimental | 35 gy of radiation therapy will be administered in 5 fractions. Receives: Radiation: 35 Gy Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of subjects with a dose-limiting toxicity related to inoperability.
Inoperability after HyPR-HN, is defined as an inability to proceed to surgery within eight weeks of radiation.
Measured: 8 Weeks
The number of subjects with a dose-limiting toxicity related to perioperative complication rates.
Severe perioperative complication rates, defined as unacceptable toxicity from initiation of treatment until 30 days postoperatively (grade 4/5 toxicity) probably or definitely related to treatment.
Measured: 8 Weeks
The number of subjects with severe delayed toxicity.
Severe delayed toxicities, defined as any unacceptable toxicity (grade 4+) after 30 days postoperatively until one year after initiation of HyPR-HN probably or definitely related to treatment.
Measured: Up to one year
Secondary outcomes (2)
Overall survival
This measure is the number of subjects alive at one year following the conclusion of scheduled radiation therapy.
Measured: One year
Recurrence-free Survival
This measure is the number of subjects who are survival free of locoregional recurrence or distant metastasis.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2022
- Study start6 Jan 2023
- Primary completion24 Aug 2026
- Study completion24 Aug 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph Zenga, Medical College of Wisconsin
- Investigators
- Joseph Zenga, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05538533
- Sponsor's protocol ID
- PRO44863
- Status last verified
- Oct 2026
- First submitted
- 9 Sep 2022
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Hypofractionated Preoperative Radiation for Head and Neck Cancers (HyPR-HN)
- ClinicalTrials.gov ID
- NCT05538533
- Acronym / sponsor ID
- PRO44863
- Conditions
- Head and Neck Cancer
- Keywords
- Head and Neck Cancer, Hypofractionated Preoperative Radiation, Time-to-Event Continuous Reassessment Methodology, TITE-CRM
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 6 Jan 2023 (actual)
- Primary completion
- 24 Aug 2026 (actual)
- Study completion
- 24 Aug 2026 (actual)
- First posted
- 14 Sep 2022 (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.
This is a phase 1 study to determine the safety of a condensed preoperative radiation regimen (10, 7, or 5 fractions) for the management of head and neck squamous cell carcinoma.
Detailed description
All subjects in this study will receive pre-operative hypofractionated radiation therapy, which will be subject to fractionation reduction, that being 10 fractions, 7 fractions, or 5 fractions, as compared to 30 fractions of conventional radiation therapy. All patients will subsequently undergo surgery for resection of remaining disease at the primary site and at-risk nodal basins 6-8 weeks after completion of radiation.
The subjects will receive smaller number of fractions (total visits) but with a higher dose of radiation with each Dose Level. Participants will receive a total radiation dose of 46 Gy in 10 fractions (Dose Level 1), 40 Gy in 7 fractions (Dose Level 2), or 35 Gy in 5 fractions (Dose Level 3), depending on the assigned experimental total fractions. Radiation will be delivered using intensity modulated radiation therapy (IMRT) with a daily cone-beam CT for five days a week, for less than two weeks depending on the assigned dose level at the time of enrollment.
Due to the novelty of translational data and non-dependency on the primary endpoint, presentation and publication in a scientific journal of the translational endpoints may precede publication of the primary endpoint.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This study will use a time-to-event continual reassessment method (TITE-CRM) for assigning subjects to the radiation therapy dosages.
| Arm | Type | Receives |
|---|---|---|
| 46 Gray (Gy) | Experimental | Radiation: 46 Gy Radiation Therapy46 gy of radiation therapy will be administered in 10 fractions. |
| 40 Gray (Gy) | Experimental | Radiation: 40 Gy Radiation Therapy40 gy of radiation therapy will be administered in 7 fractions. |
| 35 Gray (Gy) | Experimental | Radiation: 35 Gy Radiation Therapy35 gy of radiation therapy will be administered in 5 fractions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients 18 years or older with surgically resectable, Human papillomavirus (HPV) -negative squamous cell carcinoma of the head and neck (squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, nasal cavity or paranasal sinuses). Resectability will be determined by the treating surgeon. Patients must have locoregionally advanced disease defined by clinical T3-4 staging and/or clinical node positive staging. Patients may also be eligible if they meet one of the following criteria:
- Zubrod performance status 0-2.
- Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up.
- Inclusion of COVID-19 positive patients will be based on standard institutional protocol.
- Female patients must meet one of the following:
Key exclusion criteria (14 listed)
- Radiographic evidence of extranodal extension.
- Patients with laryngeal involvement who are candidates for non-surgical laryngeal preservation as deemed by a surgeon and/or radiation oncologist. These patients include, but are not limited to, those with T1-T3 laryngeal cancer who do not have pretreatment tracheostomy and/or feeding tube or those with base of tongue/hypopharyngeal cancers with laryngeal involvement without cartilage invasion or pretreatment tracheostomy and/or feeding tube.
- HPV-positive squamous cell carcinoma.
- Prior invasive malignancy within the past three years (except for non-melanomatous skin cancer, and early stage treated prostate cancer).
- Life expectancy less than 12 months.
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 |
|---|---|---|
| 46 Gy Radiation TherapyDose per fraction of 4.6. | Radiation | 46 Gray (Gy) |
| 40 Gy Radiation TherapyDose per fraction 5.7. | Radiation | 40 Gray (Gy) |
| 35 Gy Radiation TherapyDose per fraction 7.0. | Radiation | 35 Gray (Gy) |
Primary outcome
The number of subjects with a dose-limiting toxicity related to inoperability.
Time frame: 8 Weeks
Inoperability after HyPR-HN, is defined as an inability to proceed to surgery within eight weeks of radiation.
The number of subjects with a dose-limiting toxicity related to perioperative complication rates.
Time frame: 8 Weeks
Severe perioperative complication rates, defined as unacceptable toxicity from initiation of treatment until 30 days postoperatively (grade 4/5 toxicity) probably or definitely related to treatment.
The number of subjects with severe delayed toxicity.
Time frame: Up to one year
Severe delayed toxicities, defined as any unacceptable toxicity (grade 4+) after 30 days postoperatively until one year after initiation of HyPR-HN probably or definitely related to treatment.
2 secondary outcomes
Overall survival
Time frame: One year
Recurrence-free Survival
Time frame: One year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- 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.
Joseph Zenga, MD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 46 Gy Radiation Therapy, 40 Gy Radiation Therapy and 35 Gy Radiation Therapy in people with Head and Neck Cancer, run by Medical College of Wisconsin 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 17 inclusion and 14 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 16 Oct 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The number of subjects with a dose-limiting toxicity related to inoperability. (time frame: 8 Weeks). The study lists 3 primary outcomes in all. 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 16 Oct 2026.