Vocal-cord vs. Complete Laryngeal Radiotherapy for Early Glottic Cancer

Study Overview
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Brief Summary
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This is a multicentrer, randomized Bayesian Phase II trial for patients with early stage (T1N0) glottic squamous cell carcinoma treated with radical radiotherapy. The primary objective is to assess the non-inferiority of local control achieved with vocal-cord only radiotherapy (VC-RT) compared to complete larynx radiotherapy (CL-RT) in T1N0 glottic laryngeal squamous cell cancer, measured at 2-years after treatment. Secondary outcomes include overall survival, as well as voice impairment, dysphagia and quality of life, measured respectively by the voice handicap index -10 (VHI-10), the MD Anderson Dysphagia Inventory (MDADI) and the MD Anderson Symptom Inventory- Head and Neck module (MDASI-HN). Patients will be randomized in a 1:3 ratio to CL-RT (39 patients) and VC-RT (116 patients) arms. There will be stratification by tumor stage (T1a/T1b) and by institution. An interim analysis is planned after the first 55 patients enrolled on the experimental arm have a 6-month follow-up.

Official Title
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A Randomized Study of Vocal-cord Only vs. Complete Laryngeal Radiotherapy for Early Glottic Cancer

Conditions
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Cancer Neck, Larynx Cancer, Glottis Tumor

Intervention / Treatment
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* Radiation: Vocal-cord Radiotherapy
* Radiation: Complete Larynx Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage T1a-b N0 of the true vocal cords planned for definitive RT Patient not candidate for laser surgery or declined laser surgery Biopsy-confirmed squamous cell carcinoma, including verrucous carcinoma Eastern Cooperative Oncology Group performance status 0-2 Ability to provide written informed consent. Exclusion Criteria: Previous irradiation of the head and neck (HNC) region Pregnancy or breastfeeding Any medical condition that represents, in the opinion of the investigator, a contraindication to radiotherapy or would prevent follow-up after radiotherapy. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vocal-cord Radiotherapy<br> | Radiation: Vocal-cord Radiotherapy<br>* Focal radiotherapy limited to the involved vocal cord(s) plus additional margins accounting for respiration and set-up errors.<br>|
| Active Comparator: Complete Larynx Radiotherapy<br> | Radiation: Complete Larynx Radiotherapy<br>* Radiotherapy to the entire larynx, with target volumes defined to lead to traditional volumes from conventional complete larynx radiotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local control | Local control rate of vocal-cord radiotherapy | At 2-year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Voice Handicap Index-10 score | Scores are rated on a 0-4 scale to indicate the presence and severity of the symptoms. Lower scores represent better functioning and quality of life. | Week 0 post-treatment, and at 2-month, 6-month, 1-year and 2-year follow-up | 
| MD Anderson Dysphagia Inventory score | Overall score ranges from 0 to 100, with higher score representing better functioning and quality of life. | Week 0 post-treatment, and at 2-month, 6-month, 1-year and 2-year follow-up | 
| MD Anderson Symptom Inventory-Head & Neck score | The core and head and neck cancer specific symptoms are rated on a 0-10 scale to indicate the presence and severity of the symptoms. Lower scores represent better functioning and quality of life. | Week 0 post-treatment, and at 2-month, 6-month, 1-year and 2-year follow-up | 
| Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) | The attributes of CAPE-V are: (a) Overall Severity; (b) Roughness; (c) Breathiness; (d) Strain; (e) Pitch; and (f) Loudness. Each attribute is displayed accompanied by a 100- millimeter line forming a visual analog scale, with a higher score representing more deviant voice attributes. | Week 0 post-treatment and at 6-month follow-up | 
| Rates of acute toxicity as per CTCAE v5.0 |  | Week 0 post-treatment and at 2-month follow-up | 
| Rates of chronic toxicity as per CTCAE v5.0 |  | At 6-month, 1-year, 2-year and 5-year post-treatment | 
| Rates of new hypothyroidism |  | At 2- and 5-year follow-up | 
| Rates of cerebrovascular event (transient ischemic attack or stroke) |  | At 5-year follow-up | 
| Overall survival |  | At 2- and 5-year follow-up | 
| Time to recurrence |  | At 2- and 5-year follow-up |