Hypofractionated Adjuvant Radiotherapy for Resected Head and Neck Cancers

NCT05120947 | Completed Results DMC FDA Device

• 1 other identifier: PRO00042119
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Resectable Head and Neck Squamous Cell Carcinoma

Keywords

Head and Neck Squamous Cell Carcinoma; Hypofraction Adjuvant Radiation

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  12 months

Secondary Outcomes (2)

• Overall Survival

  One year

• Locoregional Progression

  One year

Study Arms (3)

42 Gray (Gy) Radiation

EXPERIMENTAL

42 gy of radiation therapy will be administered in 10 fractions.

Radiation: 42 Gy Radiation Therapy

39 Gray (Gy) Radiation

EXPERIMENTAL

39 gy of radiation therapy will be administered in 8 fractions.

Radiation: 39 Gy Radiation Therapy

32.5 Gray (Gy) Radiation

EXPERIMENTAL

32.5 gy of radiation therapy will be administered in 5 fractions.

Radiation: 32.5 Gy Radiation Therapy

Interventions

42 Gy Radiation Therapy RADIATION

Radiation Therapy: Dose per fraction of 4.2 Gy.

42 Gray (Gy) Radiation

39 Gy Radiation Therapy RADIATION

Radiation Therapy: Dose per fraction of 4.875 Gy.

39 Gray (Gy) Radiation

32.5 Gy Radiation Therapy RADIATION

Radiation Therapy: Dose per fraction of 6.5 Gy.

32.5 Gray (Gy) Radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Pathologic Node Positive Disease
• Perineural Invasion
• Oral cavity cancer with depth of invasion of at least 5 mm
• Lymphovascular Space Invasion
• 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.
• 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.)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (6)

• 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.

  PMID: 31944484 BACKGROUND

• 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.

  PMID: 28343352 BACKGROUND

• 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.

  PMID: 10618610 BACKGROUND

• 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.

  PMID: 1993628 BACKGROUND

• 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.

  PMID: 29749569 BACKGROUND

• 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.

  PMID: 32580883 BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Results Point of Contact

• Title: Musaddiq Awan, MD
• Organization: Medical College of Wisconsin

mawan@mcw.edu

414-805-4400

Study Officials

• Musaddiq Awan, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: This study will use a time-to-event continual reassessment method (TITE-CRM) for assigning subjects to the radiation therapy dosages.

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: November 16, 2021
• Study Start: December 1, 2021
• Primary Completion: March 6, 2025
• Study Completion: November 22, 2025
• Last Updated: May 1, 2026
• Results First Posted: March 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)