Hypofractionated Radiotherapy in Elderly Patients With Head & Neck Squamous Cell Carcinoma

A Non-Randomized, Open-Label, Multi-Center Pilot Study Evaluating Hypofractionation Radiation Therapy in Head and Neck Squamous Cell Carcinoma

The purpose of this research study is to investigate a shorter radiation treatment schedule for head and neck cancers in patients 70 years of age and older.

Standard radiation treatment for head and neck patients normally requires that the patient travel to the hospital daily for 6-7 weeks to receive radiation treatment 5 days per week. This long course of radiation can lead to significant side effects resulting in some people being unable to complete the course of treatment. If this happens, and there are gaps in the radiation treatment, this can lead to worse outcomes.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma (HNSCC)
• Intervention / Treatment: Radiation: Adjuvant hypofractionation; Radiation: Definitive Hypofractionation

Detailed Description

This is a non-randomized pilot study examining the objective response rate and tolerability of short-course radiotherapy (RT) in elderly patients who are unfit for standard conventional fractionation treatment with head and neck squamous cell carcinoma (HNSCC). There will be two unrelated cohorts in this study: definitive RT and adjuvant RT. Patients will be assigned to the cohorts based on their surgical or non-surgical candidacy. The primary study measure is the locoregional control (LRC) rate of patients at 6 months post RT treated with short-course RT. Locoregional control at one year will be determined by radiographic (PET/CT) and clinical assessment of disease. For the definitive cohort, LRC will be defined as regression in size or disappearance of primary tumor and/or lymph nodes on imaging or clinical examination; and for the adjuvant cohort, LRC will be defined as absence of disease on imaging or no clinical evidence of disease.

To further investigate the treatment regimen, the study team will assess the safety of short-course RT and determine the incidence of serious complications, overall survival (OS), disease-free survival (DFS) within 1 year, and the change in quality of life (QoL) in these patients who are unfit for standard conventional fractionation treatment with head and neck squamous cell carcinoma (HNSCC) as secondary objectives. Secondary endpoints will include 1- year overall survival (OS), 1-year disease-free survival (DFS), and the total score of the Functional Assessment of Cancer Therapy-Head and Neck questionnaire (FACT-H&N). DFS will be defined from the completion of treatment until disease recurrence locally, regionally and/or distantly or until death from disease. OS will be defined from the RT to death or to last follow-up.

As a safety endpoint, the study team will calculate number and proportion of patients developing reportable AEs and SAEs according to relatedness to the treatment and stratified by severity.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Richard L. Bakst, MD; Phone Number: 43545 (212) 241- 3545; Email: richard.bakst@mountsinai.org
• Study Contact Backup: Name: Lynda N. Rath; Phone Number: 57501 (212) 824-7501; Email: lynda.rath@mountsinai.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10011
      • Recruiting
      • Mount Sinai Chelsea
      • Sub-Investigator: Vishal Gupta, MD
      • Contact: Carol White; Phone Number: 212-844-8099; Email: carol.white@mountsinai.org
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Hospital
      • Contact: Lynda N. Rath; Phone Number: 57501 212-824-7501; Email: lynda.rath@mountsinai.org
      • Principal Investigator: Richard L. Bakst, MD
    • New York, New York, United States, 10019
      • Recruiting
      • Mount Sinai West
      • Contact: Carol White; Phone Number: 212-844-8099; Email: carol.white@mountsinai.org
      • Sub-Investigator: Pinaki Dutta, MD
    • New York, New York, United States, 10003
      • Recruiting
      • Mount Sinai Downtown Union Square
      • Contact: Carol White; Phone Number: 212-844-8099; Email: carol.white@mountsinai.org
      • Sub-Investigator: Jerry Liu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 68 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Age ≥ 70 years.
• No previous RT or chemotherapy for HNSCC is allowed at time of study entry.
• Life expectancy > 12 weeks.
• Participants must have histologically or cytologically confirmed diagnosis of HNSCC: oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, cervical nodes (unknown primary)
• All stages (according to National Comprehensive Cancer Network 8th edition for head and neck cancers), except stage IVC5
• Non-concurrent chemotherapy
• First line treatment
• Anyone eligible for definitive or adjuvant based RT therapy
• Adjuvant therapy when histopathological factors (advanced T category, nodal disease, lymphovascular or perineural invasion, high-grade, or positive margins)
• Anyone being treated with curative intent
• Unfit as determined by the treating physician and ECOG performance 1, 2, or 3 (Appendix 2).
• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria

• Patients < 70
• Metastatic disease outside of the head and neck
• Pregnancy
• Previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin, thyroid cancer, or other cancer curatively treated by surgery and with no current evidence of disease for at least 5 years.
• Prior RT of head and neck area
• Concurrent chemotherapy or immunotherapy or hormonotherapy
• Any comorbid connective tissue disorder which could aggravate RT associated toxicities (e.g. Scleroderma)
• In cases where patients cannot consent on their own due to underlying dementia, we can consent the patient's healthcare proxy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adjuvant Hypofractionated Radiation Treatment; Short course radiation therapy for patients who have undergone surgery	Radiation: Adjuvant hypofractionation; 15 fractions of 2.7 Gy per fraction daily over 3 weeks for a total of 40.5 Gy to the post-operative bed and/or necks.
Experimental: Definitive Hypofractionated Radiation Treatment; Short course radiation therapy for patients who have not had surgery	Radiation: Definitive Hypofractionation; 15 fractions of 3 Gy per fraction daily over 3 weeks for a total of 45 Gy to regions of gross disease. Elective areas can be treated to 37.5 Gy in 15 fractions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Locoregional Control (LRC)	For the adjuvant cohort: LRC will be defined as absence of disease on imaging or no clinical evidence of disease. For the definitive cohort: LRC will be defined as regression in size or disappearance of primary tumor and/or lymph nodes on imaging or clinical examination.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) rate	1 year overall survival of patients as defined by completion of treatment until death at 1 year.	1 year
Disease Free Survival (DFS) rate	1 year disease free survival of patients as defined by completion of treatment until disease recurrence locally, regionally and/or distantly or until the time of death due to disease assessed via PET scan and physical exam.	1 year
University of Washington Quality of Life Questionnaire (UW-QOL)	University of Washington Quality of Life Questionnaire (UW-QOL) full scale from 0 to 100, with higher score indicating poorer health outcomes.	Up to 3 years
FACT-H&N questionnaire	Foundation for the Accreditation of Cellular Therapy-Head and Neck (FACT-H&N) questionnaire, 38-item instrument. Full scale from 0 to 144, with higher score indicating better quality of life.	Up to 1 year

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Richard L. Bakst, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: February 24, 2020
• First Submitted That Met QC Criteria: February 24, 2020
• First Posted (Actual): February 25, 2020

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Elderly; Head and Neck Cancer; Radiotherapy; Head and Neck Squamous Cell Carcinoma; Over 70 years of age; shorter course of radiation treatment
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: GCO 19-0499

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All of the individual participant data collected during the trial, after deidentification.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No