Stereotactic Ablative Radiotherapy for Early-stage Glottic Larynx Cancer

A Phase II Study of Glottic Larynx Stereotactic Ablative Radiotherapy (LT-SABR) for Early-Stage Glottic Larynx Cancer

This is a prospective study to determine the local control and quality-of-life outcomes of using SBRT for early-stage glottic larynx cancer.

Study Overview

• Status: Completed
• Conditions: Glottic Carcinoma
• Intervention / Treatment: Radiation: Radiation therapy

Detailed Description

SBRT treatment will be delivered to patients diagnosed with stage I-II glottic larynx cancer twice per week for 5 fractions (42.5 Gy cohort, low-risk) or daily for 16 fractions (58.08 Gy cohort, moderate-risk).

Low-risk is defined by:

• Planning target volume (PTV) less than 10 cc, AND
• No reported smoking within 1 month from registration

Moderate-risk is defined by:

• Planning target volume (PTV) greater than or equal to 10 cc, OR
• Smoking within 1 month from registration (no more than 1 pack per day)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pathologically-proven diagnosis of squamous cell carcinoma in situ, squamous cell carcinoma or squamous cell variants (sarcomatoid, verrucous, basaloid, and papillary subtypes) involving the glottic larynx.
2. Clinical stage I-II (American Joint Committee on Cancer AJCC, 7th edition) with direct laryngoscopy showing no evidence of greater than stage II true glottic larynx cancer and PET/CT or CT neck showing no evidence of regional disease.
3. Age ≥ 18 years.
4. ECOG Performance Status 0-2

5. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

   5.1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

   • Has not undergone a hysterectomy or bilateral oophorectomy; or
   • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
6. Negative serum or urine pregnancy test within 2 weeks before registration for women of childbearing potential.
7. Ability to understand and the willingness to sign a written informed consent.
8. Patients with cognitive impairment or other limited decision making capacity with the ability to understand and willingly sign written informed consent or have the consent signed by a designated legally authorized representative (LAR)

Exclusion Criteria:

1. AJCC stage III or stage IV larynx cancer
2. Involvement of the arytenoid cartilage beyond the vocal process.
3. Prior chemotherapy for treatment of the targeted larynx lesion
4. Synchronous primaries in the head and neck
5. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields.
6. Subjects smoking in excess of 1 pack of cigarettes per day.
7. Subjects may not be receiving any other investigational agents.
8. 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.
9. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SBRT Treatment; Patients are all treated with stereotactic body radiation therapy (SBRT), using either CyberKnife or volumetric modulated arc therapy (VMAT). Dosing is based on the patients' assessed risk. The two cohorts are low risk and moderate risk. Low-risk is defined by: Planning target volume (PTV) less than 10 cc, AND; No reported smoking within 1 month from registration Radiation Therapy will be delivered twice per week for 5 fractions (total 42.5 Gy)- this provides both an adequate tumoricidal dose, and a limited dose to normal tissue. Moderate-risk is defined by: Planning target volume (PTV) greater than or equal to 10 cc, OR; Smoking within 1 month from registration (no more than 1 pack per day) Radiation Therapy will be delivered daily for 16 fraction (total 58.08 Gy)

Radiation: Radiation therapy; Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiation therapy (SBRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Local Failure Following SABR Treatment of Early Glottic Larynx Cancers	Local failure is defined as biopsy-proven tumor anywhere on the true vocal cords.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival	2 years
Voice-quality Score Following Treatment With SABR	Voice Handicap Index (VHI) voice-quality score to monitor changes in self-perception of voice handicap before and after treatment. 0-30 Mild Minimal amount of handicap 31-60 Moderate handicap 60-120 Severe handicap	From baseline to 2 years post-treatment
Number of Patients With Grade 3-5 Acute and Late Toxicities Following Treatment With SABR	Number of patients with grade 3-5 acute (start of treatment through 90 days from the completion of treatment) and late (after 90 days from the completion of treatment) adverse events, according to NCI's Common Terminology Criteria for Adverse Events (CTCAE) v4.0 toxicity criteria.	90 days, 3 years
Percentage of Participants With Locoregional Failure Following SABR With Death as a Competing Risk	Specifically, the 2-year cumulative risk of biopsy-proven recurrence anywhere in the larynx or neck following SABR. Recurrence in this context includes biopsy-proven cancer anywhere in the supraglottic, glottic, or subglottic larynx, as well as any malignant lymph node in the cervical or supraclavicular lymph nodes.	2 years
Percentage of Patient Population With Regional Failure and Distant Metastasis	With death and prior locoregional failure as competing risks	2 years
Laryngectomy-free Survival	Laryngectomy-free survival probability at 2 years	2 years
Health-related Quality of Life Following Treatment With SABR.	Average patient visual analogue scale score (derived from EQ-5D) at baseline, 6, 12, and 24 months from the end of treatment The Visual Analogue Score (VAS) of the EQ-5D is a visual scale from 0-100, with 100 being perfect health, where patients can mark their perceived health. Researchers can then take the average score across all patients for each timepoint.	From baseline to 2 years post-treatment

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: David Sher, MD, University of Texas Southwestern Medical Center

Publications and helpful links

General Publications

• Zhao B, Park YK, Gu X, Reynolds R, Timmerman R, Sher DJ. Surface guided motion management in glottic larynx stereotactic body radiation therapy. Radiother Oncol. 2020 Dec;153:236-242. doi: 10.1016/j.radonc.2020.08.027. Epub 2020 Sep 3.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2018
• Primary Completion (Actual): April 25, 2023
• Study Completion (Actual): April 30, 2024

Study Registration Dates

• First Submitted: May 3, 2018
• First Submitted That Met QC Criteria: June 6, 2018
• First Posted (Actual): June 7, 2018

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 7, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Head and Neck Neoplasms; Respiratory Tract Neoplasms; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Laryngeal Diseases; Laryngeal Neoplasms
• Other Study ID Numbers: STU 122017-043

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