Stereotactic Ablative Radiotherapy for Early-stage Glottic Larynx Cancer

Study Overview
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Brief Summary
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The goal of treatment with radiation therapy is to deliver as high of a dose as possible to the target (tumor), while minimizing the dose to the normal tissues where late-side effects can drastically affect patient quality of life.

Detailed Description
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Radiation will be delivered 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)

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

Conditions
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Glottic Carcinoma

Intervention / Treatment
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* Radiation: Radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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. Age ≥ 18 years. ECOG Performance Status 0-2 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). Negative serum or urine pregnancy test within 2 weeks before registration for women of childbearing potential. Ability to understand and the willingness to sign a written informed consent. 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: AJCC stage III or stage IV larynx cancer Involvement of the arytenoid cartilage beyond the vocal process. Prior chemotherapy for treatment of the targeted larynx lesion Synchronous primaries in the head and neck Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields. Subjects smoking in excess of 1 pack of cigarettes per day. Subjects may not be receiving any other investigational agents. 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. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: patient with low risk<br>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) | Radiation: Radiation therapy<br>* Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiation therapy (SBRT)<br>|
| Experimental: patient with moderate risk<br>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<br>* Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiation therapy (SBRT)<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Swallowing ability following treatment with SABR. | The M. D. Anderson Dysphagia Inventory (MDADI) to assess how patients view the outcome of their swallowing ability as a result of treatment and how this swallowing dysfunction affects their quality of life. MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning). MDADI is a self-administered questionnaire designed specifically for evaluating the impact of dysphagia on the quality of life of patients with head and neck cancer | 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 | 
| Health-related quality of life following treatment with SABR. | Average patient utilities (derived from EQ-5D) at baseline, 6, 12, and 24 months from the end of treatment EuroQol five dimension scale (EQ-5D) is a standardized instrument for measuring generic health status. The maximum score of 1 indicates the best health state, by contrast with the scores of individual questions, where higher scores indicate more severe or frequent problems | From baseline to 2 years post-treatment | 
| Cumulative incidence of locoregional failure following SABR | 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 | 
| Overall survival | Overall survival | 2 years | 
| Cumulative incidence of 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 |