Randomized Trial of ARCON in Larynx Cancer

Study Overview
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Brief Summary
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TITLE: A multicentre, randomised, phase III clinical trial comparing accelerated radiotherapy with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in clinical stage T2-4 laryngeal carcinoma. PRIMARY OBJECTIVE: Does the addition of carbogen and nicotinamide to a schedule of accelerated radiotherapy in patients with clinical stage T2-4 laryngeal carcinoma improve local primary tumour control? Definitive analysis will be performed on local control rates at two years after completion of radiotherapy. SECONDARY OBJECTIVES: Does the addition of carbogen and nicotinamide increase the larynx preservation rate? increase the regional control rate? increase the toxicity of accelerated radiotherapy? improve the overall quality of life? improve the disease-free survival? improve the overall survival? STUDY DESIGN: An open-label, randomised clinical trial assigning patients in a 1:1 ratio to one of the following treatment arms: accelerated radiotherapy accelerated radiotherapy plus carbogen and nicotinamide PATIENT CHARACTERISTICS AND NUMBER: 344 patients with clinical T2-4 laryngeal carcinoma MEASUREMENTS: time to local failure time to regional failure survival with functional larynx overall and disease-free survival frequency and severity of complications related to radiotherapy and carbogen and nicotinamide quality of life assessment

Official Title
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A Multicentre, Randomised, Phase III Clinical Trial Comparing Accelerated Radiotherapy With Accelerated Radiotherapy Plus Carbogen and Nicotinamide (ARCON) in Clinical Stage T2-4 Laryngeal Carcinoma.

Conditions
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Larynx Carcinoma

Intervention / Treatment
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* Radiation: Accelerated radiotherapy
* Radiation: ARCON


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological confirmed squamous cell carcinoma of the larynx. TNM-classification (UICC 1997, appendix I): T3-4 glottic or supraglottic carcinoma T2 glottic carcinoma with impaired cord mobility or subglottic extension T2 supraglottic carcinoma with invasion of mucosa of base of tongue or vallecula or invasion of the medial wall of the piriform sinus. any N-stage, M0. WHO performance status 0 or 1 (appendix II). Age > 18 years. Written informed consent. Quality of life questionnaire completed. Exclusion Criteria: Prior or concurrent treatment for this tumour. Severe stridor and adequate debulking of airway not possible. Impaired renal function: serum creatinine above upper normal limit. Use of nefrotoxic medication (including ACE-inhibitors) that cannot be discontinued for the duration of the radiation treatment. Impaired hepatic function: ASAT and ALAT more than 1.5 times the upper normal limit. Use of anti-convulsants that cannot be discontinued for the duration of the radiation treatment. History of malignancy during the previous 5 years except basal cell carcinoma of skin, carcinoma in situ of the cervix, or superficial bladder neoplasm (pTa).

Ages Eligible for Study
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Minimum Age: 19 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 |
| --- | --- |
| Active Comparator: 1<br>Accelerated radiotherapy | Radiation: Accelerated radiotherapy<br>* 68 Gy over 5.5 weeks<br>|
| Experimental: 2<br>ARCON | Radiation: ARCON<br>* 68 Gy over 5.5 weeks Carbogen: 98% oxygen plus 2% carbon dioxide Nicotinamide 60 mg/kg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local control |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| larynx preservation |  | 2 years | 
| regional control rate |  | 2 years | 
| toxicity |  | 5 years | 
| quality of life |  | 2 years | 
| disease-free survival |  | 5 years | 
| improve the overall survival |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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larynx carcinoma, radiotherapy, carbogen, nicotinamide