CyberKnife Accelerated Hemilarynx Stereotactic Radiotherapy Study for Early-stage Glottic Larynx Cancer

A Phase I CyberKnife Accelerated Hemilarynx Stereotactic Radiotherapy Study for Early-stage Glottic Larynx Cancer

The feasibility of reducing fractions in early-stage laryngeal cancer has not previously been prospectively studied, and we will therefore conduct a careful phase I bio-equivalent dose fraction reduction study.

Study Overview

• Status: Completed
• Conditions: Early-stage Glottic Larynx Cancer
• Intervention / Treatment: Radiation: CyberKnife Accelerated Hemilarynx Stereotactic Radiotherapy

Detailed Description

Patients enrolled at each dose level will undergo routine evaluations to identify potential toxicities as well functional voice analyses. Adequate waiting periods will be used to ensure that fraction reduction does not proceed prior to observing toxicity. The purpose of the study will be either to determine the maximal fraction reduction possible until a dose is reached where a dose-limiting toxicity occurs. The initial dose and fractionation will be 50 Gy in 15 fractions with the goal to reduce number of fractions to a dose of 42.5 Gy in 5 fractions. The rationale for using 5 fractions is that it is tolerated in centrally located lung tumors at a dose of 50 Gy in 5 fractions, and thus, is likely to be tolerated in large calliber airways.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75239
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

3.1.1 Stage Tis, T1, or T2 laryngeal squamous cancer as defined by American Joint Commission on Cancer (AJCC) 2007 staging system

3.1.2 Biopsy proven squamous cell carcinoma histology or squamous cell variants (sarcomatoid, verrucous, basaloid, and papillary subtypes) involving the true vocal cord

3.1.3 Direct laryngoscopy showing no evidence of greater than Stage II true glottic larynx cancer

3.1.4 PET/CT, X-ray, CT-scan of the chest showing no evidence of metastatic disease

3.1.5 PET/CT or CT-scan of the neck showing no evidence of nodal involvement

3.1.6 Age ≥ 18 years.

3.1.7 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.

3.1.7.1 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).

3.1.8 Ability to understand and the willingness to sign a written informed consent

3.1.9 Eastern Cooperative Oncology Group (ECOG) performance status 0-1

3.1.10 Negative Urine β-HCG or negative serum quantitative β-HCG or within 2 weeks prior to registration for women of childbearing potential

Exclusion Criteria:

3.2.1 Evidence of fixed vocal cord (Stage cT3)

3.2.2 Evidence of thyroid or soft tissue invasion (Stage cT4)

3.2.3 Evidence of positive nodal disease (Stage N1)

3.2.4 Evidence of metastatic disease (Stage M1)

3.2.5 Subjects may not be receiving any other investigational agents.

3.2.6 Non-squamous histology including lymphoma, neuroendocrine carcinoma, adenocarcinoma, or other histology.

3.2.7 Previous laryngeal surgery.

3.2.8 Previous laser therapy within one year prior to protocol treatment.

3.2.9 Previous head and neck radiation therapy involving the glottic larynx

3.2.10 Patients with collagen vascular disease, specifically dermatomyositis with a CPK level above normal or active skin rash, systemic lupus erythematosis, or scleroderma.

3.2.11 Any prior treatment with radiation therapy or chemotherapy for the currently diagnosed larynx cancer prior to registration.

3.2.12 History of another active uncontrolled malignancy at the time of study enrollment

3.2.13 Subjects must not be pregnant due to the potential for congenital abnormalities.

3.2.14 Patients smoking in excess of 2 packs of cigarettes per day.

3.2.15 ECOG performance status ≥ 2

3.2.16 Life expectancy < 3 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiation; CyberKnife Accelerated Hemilarynx Stereotactic Radiotherapy	Radiation: CyberKnife Accelerated Hemilarynx Stereotactic Radiotherapy; CyberKnife Accelerated Hemilarynx Stereotactic Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fraction	To determine the feasibility of fraction reduction for early-stage laryngeal cancer without exceeding the maximum tolerated dose.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	To determine overall survival at 5 years	5 years
loco-regional control	To determine loco-regional control at 5 years as determined by physical exam, visualization of tumor by layngoscopy, and CT-scan of the neck to determine if the primary tumor is controlled. A tissue biopsy or recurrent or persistent disease will be required to be considered a loco-regional failure.	5 years
functional voice quality	To characterize functional voice quality of patients treated on this protocol.	18 months
Quality of Life	To characterize the HR-QoL and PRO of patients treated on this protocol.	18 months
cost-effectiveness	To determine cost-effectiveness of hypofractionated larynx irradiation	18 months
late toxicity	To determine late toxicity as defined as treatment-related toxicity occurring ≥ 18 months from completion of radiation therapy.	18 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Baran Sumer, MD, UTSW

Publications and helpful links

General Publications

• Zhang Y, Chiu T, Dubas J, Tian Z, Lee P, Gu X, Yan Y, Sher D, Timmerman R, Zhao B. Benchmarking techniques for stereotactic body radiotherapy for early-stage glottic laryngeal cancer: LINAC-based non-coplanar VMAT vs. Cyberknife planning. Radiat Oncol. 2019 Nov 4;14(1):193. doi: 10.1186/s13014-019-1404-z.
• Schwartz DL, Sosa A, Chun SG, Ding C, Xie XJ, Nedzi LA, Timmerman RD, Sumer BD. SBRT for early-stage glottic larynx cancer-Initial clinical outcomes from a phase I clinical trial. PLoS One. 2017 Mar 2;12(3):e0172055. doi: 10.1371/journal.pone.0172055. eCollection 2017.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2013
• Primary Completion (Actual): May 31, 2022
• Study Completion (Actual): May 31, 2022

Study Registration Dates

• First Submitted: November 7, 2013
• First Submitted That Met QC Criteria: November 7, 2013
• First Posted (Estimate): November 14, 2013

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Larynx Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Respiratory Tract Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Otorhinolaryngologic Diseases; Laryngeal Neoplasms; Laryngeal Diseases
• Other Study ID Numbers: STU 062013-052