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VoiceS: Voice Quality After Transoral CO2-Laser Surgery Versus Single Vocal Cord Irradiation for Larynx Cancer (VoiceS)

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ClinicalTrials.gov Identifier: NCT04057209
Recruitment Status : Recruiting
First Posted : August 15, 2019
Last Update Posted : May 19, 2022
Sponsor:
Collaborators:
University of Bern
The Netherlands Cancer Institute
University of Lausanne Hospitals
University Hospital, Geneva
University of Zurich
Information provided by (Responsible Party):
Olgun Elicin, University Hospital Inselspital, Berne

Brief Summary:

Laser surgery and radiotherapy are well-established standards of care for unilateral stage 0 & I carcinoma in situ (Cais) and squamous cell carcinoma of glottic larynx (SCCGL). Based on meta-analyses, functional and oncological outcome after both treatment modalities are comparable1-5. However, no properly conducted randomized trials comparing these treatments exist. The only such trial with the endpoint of voice quality had to be prematurely closed due to low accrual6.

The traditional radiotherapy involves the treatment of the whole larynx. Recently, a new radiotherapy technique was introduced by a team of researchers from Netherlands, where the treated target volume consists of involved vocal cord and therefore 8 to 10-fold smaller than the target volumes used for traditional whole larynx irradiation. The treatment is reduced to 16 fractions which corresponds to 3 weeks and a day7-12. The results of a prospective cohort (n=30) with single vocal cord irradiation (SVCI) were compared with the results of a historical prospective cohort previously treated with whole larynx radiotherapy (n=131) in the same institute. The median follow-up was 30 months. The voice handicap index (VHI) at all time points beginning from the 6th week after SVCI was significantly superior to the same time points with conventional radiotherapy. Moreover, a comparable local control with SVCI (100%) vs. conventional radiotherapy (92%) was reported at two years, p=0.2412.

Based on this information, the investigators' main aim is to compare SVCI to Transoral CO2-Laser Microsurgical Cordectomy (TLM) with the main focus of patient-reported voice quality.


Condition or disease Intervention/treatment Phase
Glottis Tumor Larynx Cancer Radiation: Single Vocal Cord Irradiation (SVCI) Procedure: Arm A: Transoral CO2-Laser Microsurgical Cordectomy (TLM) Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: The secondary phoniatric assessments will be carried out centrally by blinded phoniatricians.
Primary Purpose: Treatment
Official Title: VoiceS: Voice Quality After Transoral CO2-Laser Surgery Versus Single Vocal Cord Irradiation for Unilateral Stage 0 & I Glottic Larynx Cancer - A Randomized Phase III Trial
Actual Study Start Date : November 20, 2019
Estimated Primary Completion Date : November 30, 2025
Estimated Study Completion Date : November 30, 2028

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm A: Transoral CO2-Laser Microsurgical Cordectomy (TLM)
Transoral CO2-Laser Microsurgical Cordectomy defined by European Laryngological Society (Remacle M, Eckel HE, Antonelli A, et al. Endoscopic cordectomy. A proposal for a classification by the Working Committee, European Laryngological Society. Eur Arch Otorhinolaryngol. 2000;257(4):227-231.)
Procedure: Arm A: Transoral CO2-Laser Microsurgical Cordectomy (TLM)

The TLM has to be performed using a CO2 laser, coupled to an operative microscope, at 4-8W in ultrapulse mode. The type of cordectomy performed must be mentioned using the following classification according the classification of the European Laryngological Society.

The type of resection chosen should provide complete removal of the primary lesion with negative margins.

Surgery will generally be performed within 3 weeks after randomization and not more than 6 weeks after panendoscopy.

The extent of the cordectomy must include a complete anterior, posterior, inferior and supero-lateral mucosal and deep soft tissue margin.


Experimental: Arm B: Single Vocal Cord Irradiation (SVCI)
Single Vocal Cord Irradiation defined by Kwa et al. and Al-Mamgani et al. (Kwa SLS, Al-Mamgani A, Osman SOS, Gangsaas A, Levendag PC, Heijmen BJM. Inter- and Intrafraction Target Motion in Highly Focused Single Vocal Cord Irradiation of T1a Larynx Cancer Patients. Int J Radiat Oncol Biol Phys. 2015;93(1):190-195. Al-Mamgani A, Kwa SLS, Tans L, et al. Single Vocal Cord Irradiation: Image Guided Intensity Modulated Hypofractionated Radiation Therapy for T1a Glottic Cancer: Early Clinical Results. Int J Radiat Oncol Biol Phys. 2015;93(2):337-343.)
Radiation: Single Vocal Cord Irradiation (SVCI)
The following planning aim will be pursued: full coverage of the PTV with at least 95% of the prescribed dose and a maximum (0.03 cc) PTV dose of <107%: 16 x 3.63 = 58.08 Gy in 5 fractions per week using 5 to 9 static IMRT or VMAT.




Primary Outcome Measures :
  1. Voice Handicap Index [ Time Frame: 2 years ]
    average of the VHI scores (range: 0-120) of each patient up to 24 months after randomization


Secondary Outcome Measures :
  1. Roughness - Breathiness - Hoarseness (RBH) [ Time Frame: 2 years ]
    The perceptual impression of a vocal signal remains the gold standard in phoniatric diagnosis. By means of reading the phonetically balanced text "The Rainbow Passage" in English and "Die Sonne und der Wind" in German, French and Italian (versions in different languages provided in the protocol), the speaking voice is assessed by the investigator according to the parameters roughness - breathiness - hoarseness (RBH), using the scale of 0: normal, 1: mild, 2: moderate, 3: severe. In this study, the assessment will be carried out blind.

  2. Jitter and shimmer (JS) [ Time Frame: 2 years ]
    JS are regarded as objective, quantitative characteristics of voice quality. They describe the variations in the fundamental note of a vocal signal. Jitter is the variation of the cycle-to-cycle frequency in held vowels (in Hz or. %, norm = 0-3%), shimmer is the cycle-to-cycle variation in the amplitude of held vowels (in dB, or. %, norm = 0-20%). In this study, the assessment will be carried out blind.

  3. Glottal-to-Noise Excitation Ratio (GNE) [ Time Frame: 2 years ]
    GNE serves to describe the relationship of the voice signal to the noise signal (norm = 1-0) and is also a quantitative characteristic of voice quality. Jitter, shimmer and GNE correspond to the perceptual characteristics roughness - breathiness - hoarseness. In order to carry out jitter, shimmer and GNE, the test subjects hold the vowel /a/ mezzoforte for at least 5 seconds at their average speaking pitch. The vocal samples will be recorded and subsequently evaluated using the open source freeware software Praat (http://www.fon.hum.uva.nl/praat/ by Paul Boersma and David Weenink - Phonetic Sciences, University of Amsterdam Spuistraat 210 1012VT Amsterdam, Netherlands). In this study, the assessment will be carried out blind.

  4. Singing Power Ratio (SPR) [ Time Frame: 2 years ]
    The 'brilliant' sound of a voice is characterized in acoustic terms by a high degree of acoustic energy above 2 kHz. This can be calculated with the aid of the SPR. In the Fast-Fourier-Transformation, the amplitudes of the highest peaks between 2 and 4 kHz and of the highest peaks between 0 and 2 kHz are determined using a vocal sample and the one subtracted from the other. The lower the SPR, the more "sonorous" is the voice. For this, the test subjects hold the vowel /a/ mezzoforte for at least 5 seconds at their average speaking pitch. The vocal samples will be recorded and subsequently evaluated using Praat. In this study, the assessment will be carried out blind.

  5. Loco-regional control of the disease [ Time Frame: 5 years ]

    Event: loco-regional failure after randomization

    The time-to-event outcome loco-regional control will be evaluated using Kaplan-Meier curves and a Cox model adjusted for the randomization stratification factors.


  6. Toxicity / Morbidity [ Time Frame: 5 years ]

    Treatment toxicity up to 5 years (based on CTCAE v.5.0) after randomization

    Treatment toxicity up to 5 years will be summarized descriptively for each group, showing the overall number of events as well as number and percentage of patients with events.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  1. ECOG performance status 0-1 at the time of registration
  2. ≥18 years of age
  3. Baseline assessments and documentation of voice quality by means of VHI, JS, RBH, GNE, SPR.
  4. No infection hampering the voice quality at the time of voice assessment
  5. Histopathologically confirmed, previously untreated unilateral (cT1a or unilateral cTis) stage 0 or I glottic larynx cancer based on the UICC staging system (8th edition).
  6. No involvement of the anterior commissure by the tumor
  7. No previous surgery or radiotherapy to larynx
  8. No synchronous or previous malignancies. Exceptions are adequately treated basal cell carcinoma or SCC of the skin, or in situ carcinoma of the cervix uteri, low-risk prostate cancer or breast with a cancer-free follow-up time of at least 3 years, or other previous malignancy with a progression-free interval of at least 5 years.
  9. History and physical examination by treating physician (head and neck surgeon and radiation oncologist) within 28 days prior registration.
  10. The patient must be expected to withstand both study interventions
  11. The patient must have undergone panendoscopy with assessment for the feasibility of transoral exposure for resection. Patients within exposure is not feasible are not eligible.
  12. Localization of the tumor should allow resection with a minimum of 2-mm macroscopical margin without extension to the contralateral vocal fold, without partial resection of the arytenoid cartilage and without resection of parts of thyroid cartilage (Cordectomy Type I-IV according the classification of the European Laryngological Society)
  13. Hemoglobin ≥10 g/dL or 6.2 mmol/L (Note: The use of transfusion to achieve Hgb ≥10 g/dL is acceptable) within the 28 days prior to accrual
  14. Women with child-bearing potential and using effective contraception, and not pregnant and agree not to become pregnant during participation in the trial and 3 months after radiotherapy. A negative pregnancy test before inclusion (within 28 days) into the trial is required for all women with child-bearing potential. Men agree not to father a child during participation in the trial and 3 months after radiotherapy.
  15. No co-existing disease prejudicing survival (expected survival less than 6 months).
  16. No active bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  17. No history of any voice disorders lasting longer than 3 weeks
  18. No illness requiring hospitalization or precluding study therapy within 28 days before registration.
  19. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  20. Written informed consent, signed by the patient and the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04057209


Contacts
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Contact: Olgun Elicin, M.D. +41 31 632 26 32 olgun.elicin@insel.ch
Contact: Timo Nannen +41 31 63 2 90 74 timo.nannen@insel.ch

Locations
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Switzerland
CHUV Recruiting
Lausanne, Vaud, Switzerland
Contact: Jean Bourhis, MD    +41 21 314 46 66    jean.bourhis@chuv.ch   
Contact: Mahmut E Ozsahin, MD    +41 21 314 46 03    esat-mahmut.ozsahin@chuv.ch   
Principal Investigator: Jean Bourhis, MD         
Sub-Investigator: Mahmut E Ozsahin, MD         
Inselspital, Bern University Hospital Recruiting
Bern, Switzerland, 3010
Contact: Olgun Elicin, MD    +41 31 632 26 32    olgun.elicin@insel.ch   
Contact: Timo Nannen       timo.nannen@insel.ch   
Principal Investigator: Olgun Elicin, MD         
Genève University Hospital Recruiting
Geneva, Switzerland
Contact: Francesca Caparrotti, MD    +41 79 553 56 12    francesca.caparrotti@hcuge.ch   
Contact: Laurence Zulianello       Laurence.Zulianello@hcuge.ch   
Principal Investigator: Francesca Caparrotti, MD         
Sponsors and Collaborators
Olgun Elicin
University of Bern
The Netherlands Cancer Institute
University of Lausanne Hospitals
University Hospital, Geneva
University of Zurich
Investigators
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Principal Investigator: Olgun Elicin, M.D. Inselspital, Bern University Hospital, 3010 Bern, Switzerland
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Responsible Party: Olgun Elicin, Principal Investigator and Sponsor, University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT04057209    
Other Study ID Numbers: KEK-BE 2019-01506
First Posted: August 15, 2019    Key Record Dates
Last Update Posted: May 19, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: After the finalization of the study, anonymized IPD will be shared upon reasonable request.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Olgun Elicin, University Hospital Inselspital, Berne:
head and neck cancer
squamous cell carcinoma
carcinoma in situ
radiotherapy
surgery
transoral laser microsurgery
patient reported outcome
quality of life
voice
Additional relevant MeSH terms:
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Laryngeal Neoplasms
Laryngeal Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Respiratory Tract Neoplasms