CompletedNCT05120947HART-HNUpdated May 1, 2026Results posted

Hypofractionated Adjuvant Radiotherapy for Resected Head and Neck Cancers

An interventional study of 42 Gy Radiation Therapy and 39 Gy Radiation Therapy in Resectable Head and Neck Squamous Cell Carcinoma, sponsored by Medical College of Wisconsin. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-01.

Sponsored by Medical College of Wisconsin · Not applicable, Interventional, and Treatment

Phase: Not applicable
Study type: Interventional
Enrollment: 18
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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.

Read the 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)

Conditions studied

Resectable Head and Neck Squamous Cell Carcinoma

Browse trials for

Squamous Cell Carcinoma of Head and Neck 1,680

Keywords

Head and Neck Squamous Cell Carcinoma
Hypofraction Adjuvant Radiation

In context

Squamous Cell Carcinoma of Head and Neck

1,680 studies on the registry are indexed under Squamous Cell Carcinoma of Head and Neck; 539 are open to participants now.

This study's enrollment of 18 is below the median of 49 across 1,432 interventional studies indexed under Squamous Cell Carcinoma of Head and Neck.

Browse Squamous Cell Carcinoma of Head and Neck studies →

Lead sponsor

Medical College of Wisconsin is the lead sponsor of 540 studies on the registry; 120 are open to participants now.

Of its 71 completed or terminated interventional studies of FDA-regulated products, 56 (79%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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
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:
- 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).
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.)
Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion criteria

Exclusion Criteria:

Pathologic evidence of extranodal extension.
Pathologic evidence of a final positive margin (R1 resection) or gross residual disease (R2 resection).
HPV-positive squamous cell carcinoma.
Prior invasive malignancy within the past 3 years (except for non-melanomatous skin cancer, and early stage treated prostate cancer).
Life expectancy less than 12 months.
Performance status Zubrod ≥ 3.
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 3 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 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.

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 18 participants (actual)

Study arms

Experimental
42 Gray (Gy) Radiation
42 gy of radiation therapy will be administered in 10 fractions.
Radiation: 42 Gy Radiation Therapy
Experimental
39 Gray (Gy) Radiation
39 gy of radiation therapy will be administered in 8 fractions.
Radiation: 39 Gy Radiation Therapy
Experimental
32.5 Gray (Gy) Radiation
32.5 gy of radiation therapy will be administered in 5 fractions.
Radiation: 32.5 Gy Radiation Therapy

Interventions

Radiation42 Gy Radiation Therapy
Radiation Therapy: Dose per fraction of 4.2 Gy.
Radiation39 Gy Radiation Therapy
Radiation Therapy: Dose per fraction of 4.875 Gy.
Radiation32.5 Gy Radiation Therapy
Radiation Therapy: Dose per fraction of 6.5 Gy.

What researchers measure

Primary outcomes

Maximum-tolerated Radiation Dose
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.
Time frame: 12 months
Incidence of Dose-Limiting Toxicities
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.
Time frame: 12 months

Secondary outcomes

Overall Survival
This measure is the number of subjects alive at one year following the conclusion of scheduled radiation therapy.
Time frame: One year
Locoregional Progression
This measure is the number of subjects showing disease progression in the head and neck by response evaluation criteria in solid tumors (RECIST) criteria.
Time frame: One year

Results

Posted Mar 17, 2026

Participant flow

Participant flow — Overall Study
Milestone	42 Gray (Gy) Radiation	39 Gray (Gy) Radiation	32.5 Gray (Gy) Radiation
Started	3	4	11
Completed	3	3	11
Not completed	0	1	0

Outcome measures

PrimaryMaximum-tolerated Radiation Dose

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.

Time frame:: 12 months
Reported as:: Number · Gy

Maximum-tolerated Radiation Dose
Gy	Maximum Tolerated Dose
Maximum-tolerated Radiation Dose	32.5

PrimaryIncidence of Dose-Limiting Toxicities

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.

Time frame:: 12 months
Reported as:: Count of participants · Participants

Incidence of Dose-Limiting Toxicities
Participants	42 Gray (Gy) Radiation	39 Gray (Gy) Radiation	32.5 Gray (Gy) Radiation
Incidence of Dose-Limiting Toxicities	0	0	0

SecondaryOverall Survival

This measure is the number of subjects alive at one year following the conclusion of scheduled radiation therapy.

Time frame:: One year
Reported as:: Number · percentage of subjects surviving

Overall Survival
percentage of subjects surviving	42 Gray (Gy) Radiation	39 Gray (Gy) Radiation	32.5 Gray (Gy) Radiation
Overall Survival	100	100	81.8

SecondaryLocoregional Progression

This measure is the number of subjects showing disease progression in the head and neck by response evaluation criteria in solid tumors (RECIST) criteria.

Time frame:: One year
Reported as:: Number · percentage of subjects progressing

Locoregional Progression
percentage of subjects progressing	42 Gray (Gy) Radiation	39 Gray (Gy) Radiation	32.5 Gray (Gy) Radiation
Locoregional Progression	0	0	18.1

Adverse events

Collected over Up to 12 months.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
42 Gray (Gy) Radiation	0/3 (0%)	0/3 (0%)	3/3 (100%)
39 Gray (Gy) Radiation	0/3 (0%)	1/3 (33.3%)	3/3 (100%)
32.5 Gray (Gy) Radiation	2/11 (18.2%)	3/11 (27.3%)	11/11 (100%)

Most frequent serious events

Showing 10 of 15

Most frequent serious events
Event	42 Gray (Gy) Radiation	39 Gray (Gy) Radiation	32.5 Gray (Gy) Radiation
Abdominal painGastrointestinal disorders	0/3	1/3	0/11
ConstipationGastrointestinal disorders	0/3	1/3	0/11
IleusGastrointestinal disorders	0/3	1/3	0/11
DehydrationMetabolism and nutrition disorders	0/3	1/3	0/11
HyponatremiaMetabolism and nutrition disorders	0/3	1/3	0/11
HypertensionVascular disorders	0/3	1/3	0/11
Respiratory failureRespiratory, thoracic and mediastinal disorders	0/3	1/3	0/11
Tracheal stenosisRespiratory, thoracic and mediastinal disorders	0/3	1/3	0/11
DysphagiaGastrointestinal disorders	0/3	0/3	2/11
Weight LossInvestigations	0/3	0/3	1/11

Most frequent other events

Showing 10 of 138

Most frequent other events
Event	42 Gray (Gy) Radiation	39 Gray (Gy) Radiation	32.5 Gray (Gy) Radiation
Dermatitis radiationInjury, poisoning and procedural complications	3/3	3/3	5/11
Dry mouthGastrointestinal disorders	3/3	3/3	9/11
DysphagiaGastrointestinal disorders	3/3	2/3	11/11
FatigueGeneral disorders	3/3	3/3	8/11
Mucositis oralGastrointestinal disorders	3/3	3/3	11/11
NauseaGastrointestinal disorders	2/3	3/3	1/11
Neck edemaGeneral disorders	1/3	3/3	2/11
Oral painGastrointestinal disorders	3/3	3/3	5/11
Sore throatRespiratory, thoracic and mediastinal disorders	3/3	1/3	6/11
Weight lossInvestigations	2/3	3/3	8/11

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	42 Gray (Gy) Radiation	39 Gray (Gy) Radiation	32.5 Gray (Gy) Radiation	Total
<=18 years	0	0	0	0
Between 18 and 65 years	1	2	3	6
>=65 years	2	2	8	12

Sex: Female, Male
Sex: Female, Male(Participants)	42 Gray (Gy) Radiation	39 Gray (Gy) Radiation	32.5 Gray (Gy) Radiation	Total
Female	1	3	4	8
Male	2	1	7	10

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	42 Gray (Gy) Radiation	39 Gray (Gy) Radiation	32.5 Gray (Gy) Radiation	Total
Hispanic or Latino	0	0	0	0
Not Hispanic or Latino	3	4	11	18
Unknown or Not Reported	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	42 Gray (Gy) Radiation	39 Gray (Gy) Radiation	32.5 Gray (Gy) Radiation	Total
American Indian or Alaska Native	0	0	0	0
Asian	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	0	0	0	0
White	3	4	11	18
More than one race	0	0	0	0
Unknown or Not Reported	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	42 Gray (Gy) Radiation	39 Gray (Gy) Radiation	32.5 Gray (Gy) Radiation	Total
United States	3	4	11	18

Study locations

1 site

Froedtert & the Medical College of Wisconsin
Milwaukee, Wisconsin 53226, United States

References and documents

Publications

Moran MS, Truong PT. Hypofractionated radiation treatment for breast cancer: The time is now. Breast J. 2020 Jan;26(1):47-54. doi: 10.1111/tbj.13724. Epub 2020 Jan 15. PubMed 31944484 ↗
Benjamin LC, Tree AC, Dearnaley DP. The Role of Hypofractionated Radiotherapy in Prostate Cancer. Curr Oncol Rep. 2017 Apr;19(4):30. doi: 10.1007/s11912-017-0584-7. PubMed 28343352 ↗
Stevens G, Thompson JF, Firth I, O'Brien CJ, McCarthy WH, Quinn MJ. Locally advanced melanoma: results of postoperative hypofractionated radiation therapy. Cancer. 2000 Jan 1;88(1):88-94. doi: 10.1002/(sici)1097-0142(20000101)88:13.0.co;2-k. PubMed 10618610 ↗
Tupchong L, Scott CB, Blitzer PH, Marcial VA, Lowry LD, Jacobs JR, Stetz J, Davis LW, Snow JB, Chandler R, et al. Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03. Int J Radiat Oncol Biol Phys. 1991 Jan;20(1):21-8. doi: 10.1016/0360-3016(91)90133-o. PubMed 1993628 ↗
Kumar AMS, Miller J, Hoffer SA, Mansur DB, Coffey M, Lo SS, Sloan AE, Machtay M. Postoperative hypofractionated stereotactic brain radiation (HSRT) for resected brain metastases: improved local control with higher BED10. J Neurooncol. 2018 Sep;139(2):449-454. doi: 10.1007/s11060-018-2885-6. Epub 2018 May 10. PubMed 29749569 ↗
Murray Brunt A, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, Chan C, Churn M, Cleator S, Coles CE, Goodman A, Harnett A, Hopwood P, Kirby AM, Kirwan CC, Morris C, Nabi Z, Sawyer E, Somaiah N, Stones L, Syndikus I, Bliss JM, Yarnold JR; FAST-Forward Trial Management Group. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020 May 23;395(10237):1613-1626. doi: 10.1016/S0140-6736(20)30932-6. Epub 2020 Apr 28. PubMed 32580883 ↗

Study documents

Protocol and statistical analysis plan · May 11, 2022
Informed consent form · Oct 23, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 1, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05120947
Lead sponsor: Medical College of Wisconsin
Responsible party: Musaddiq Awan (Assistant Professor, Medical College of Wisconsin) — Principal investigator
First posted: Nov 16, 2021
Start date: Dec 1, 2021
Primary completion: Mar 6, 2025
Completion: Nov 22, 2025
Results posted: Mar 17, 2026
Last update: May 1, 2026

Study contacts

Musaddiq Awan, MD

principal investigator · Medical College of Wisconsin

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: Yes

View the source record on ClinicalTrials.gov ↗

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