Cevimeline in Treating Patients With Dry Mouth Caused by Radiation Therapy for Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Cevimeline may be effective in treating dry mouth that is caused by radiation therapy for head and neck cancer. It is not yet known if cevimeline is more effective than no therapy in treating dry mouth caused by radiation therapy. PURPOSE: Randomized phase III trial to determine the effectiveness of cevimeline in treating patients who have dryness of the mouth caused by radiation therapy for head and neck cancer.

Detailed Description
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OBJECTIVES: Compare the efficacy of cevimeline vs placebo, in terms of dryness of the oral cavity and salivary flow, in patients with xerostomia secondary to radiotherapy for cancers in the head and neck region. Assess the safety of this drug in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral cevimeline 3 times daily for 12 weeks in the absence of unacceptable toxicity. Arm II: Patients receive oral placebo as in arm I. PROJECTED ACCRUAL: A total of 280 patients (140 per arm) will be accrued for this study.

Official Title
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A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Cevimeline in the Treatment of Xerostomia Secondary to Radiation Therapy for Cancer in the Head and Neck Region

Conditions
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Head and Neck Cancer, Oral Complications, Radiation Toxicity

Intervention / Treatment
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* Drug: cevimeline hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Received more than 4,000 cGy of prior external beam radiotherapy for cancer in the head and neck region Radiotherapy completed more than 4 months prior to study Clinically significant salivary gland dysfunction with grade 2 or 3 xerostomia At least 1 anatomically intact parotid gland No suspected or confirmed bilateral physical closure of salivary gland ducts No history of primary or secondary Sjogren's syndrome or other underlying systemic illness known to cause xerostomia independent of prior radiotherapy exposure PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% ECOG 0-2 Life expectancy: At least 6 months Hematopoietic: Hemoglobin at least 9.0 g/dL No anemia Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) SGOT/SGPT no greater than 2 times ULN Lactate dehydrogenase no greater than 2 times ULN No evidence of active liver disease Renal: Creatinine no greater than 2.5 mg/dL BUN no greater than 50 mg/dL No history of nephrolithiasis within the past 6 months Cardiovascular: No history of significant cardiovascular disease No active congestive heart failure No uncontrolled angina No significant arrhythmia No myocardial infarction within the past 6 months Pulmonary: No history of significant pulmonary disease No controlled or uncontrolled asthma No chronic bronchitis or chronic obstructive pulmonary disease that would limit avocational activities Gastrointestinal: No history of significant gastrointestinal disorder No active pancreatic disease No gastroduodenal ulcers within the past 6 months No hypersensitive bowel conditions requiring pharmacologic therapy No inflammatory bowel disease No history of cholelithiasis within the past 6 months (unless cholecystectomy performed) Other: No clinically significant laboratory abnormality No history of alcohol or drug abuse within the past 6 months that would preclude study No prior or concurrent acute iritis or narrow-angle (angle closure) glaucoma Not pregnant Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No concurrent radiotherapy Surgery: Not specified Other: At least 30 days since other investigational new drug At least 4 weeks since prior systemic or ophthalmic pilocarpine No prior cevimeline No concurrent hyperbaric oxygen therapy No concurrent beta adrenergic antagonists, anticholinergic agents, cevimeline metabolism inhibitors, or other medications known to effect salivary function No other concurrent investigational drugs

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: Supportive Care


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cevimeline hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I salivary gland cancer, stage II salivary gland cancer, stage III salivary gland cancer, stage IV salivary gland cancer, recurrent salivary gland cancer, untreated metastatic squamous neck cancer with occult primary, recurrent metastatic squamous neck cancer with occult primary, metastatic squamous neck cancer with occult primary squamous cell carcinoma, oral complications, stage I squamous cell carcinoma of the lip and oral cavity, stage I basal cell carcinoma of the lip, stage I verrucous carcinoma of the oral cavity, stage I mucoepidermoid carcinoma of the oral cavity, stage I adenoid cystic carcinoma of the oral cavity, stage II squamous cell carcinoma of the lip and oral cavity, stage II basal cell carcinoma of the lip, stage II verrucous carcinoma of the oral cavity, stage II mucoepidermoid carcinoma of the oral cavity, stage II adenoid cystic carcinoma of the oral cavity, stage III squamous cell carcinoma of the lip and oral cavity, stage III basal cell carcinoma of the lip, stage III verrucous carcinoma of the oral cavity, stage III mucoepidermoid carcinoma of the oral cavity, stage III adenoid cystic carcinoma of the oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage IV basal cell carcinoma of the lip, stage IV verrucous carcinoma of the oral cavity, stage IV mucoepidermoid carcinoma of the oral cavity, stage IV adenoid cystic carcinoma of the oral cavity, recurrent squamous cell carcinoma of the lip and oral cavity, recurrent basal cell carcinoma of the lip, recurrent verrucous carcinoma of the oral cavity, recurrent mucoepidermoid carcinoma of the oral cavity, recurrent adenoid cystic carcinoma of the oral cavity, stage I squamous cell carcinoma of the oropharynx, stage I lymphoepithelioma of the oropharynx, stage II squamous cell carcinoma of the oropharynx, stage II lymphoepithelioma of the oropharynx, stage III squamous cell carcinoma of the oropharynx, stage III lymphoepithelioma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage IV lymphoepithelioma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx, recurrent lymphoepithelioma of the oropharynx, stage I squamous cell carcinoma of the nasopharynx, stage I lymphoepithelioma of the nasopharynx, stage II squamous cell carcinoma of the nasopharynx, stage II lymphoepithelioma of the nasopharynx, stage III squamous cell carcinoma of the nasopharynx, stage III lymphoepithelioma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, stage IV lymphoepithelioma of the nasopharynx, recurrent squamous cell carcinoma of the nasopharynx, recurrent lymphoepithelioma of the nasopharynx, stage I squamous cell carcinoma of the hypopharynx, stage II squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the hypopharynx, stage I squamous cell carcinoma of the larynx, stage I verrucous carcinoma of the larynx, stage II squamous cell carcinoma of the larynx, stage II verrucous carcinoma of the larynx, stage III squamous cell carcinoma of the larynx, stage III verrucous carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage IV verrucous carcinoma of the larynx, recurrent squamous cell carcinoma of the larynx, recurrent verrucous carcinoma of the larynx, stage I squamous cell carcinoma of the paranasal sinus and nasal cavity, stage I inverted papilloma of the paranasal sinus and nasal cavity, stage I midline lethal granuloma of the paranasal sinus and nasal cavity, stage I esthesioneuroblastoma of the paranasal sinus and nasal cavity, stage II squamous cell carcinoma of the paranasal sinus and nasal cavity, stage II inverted papilloma of the paranasal sinus and nasal cavity, stage II midline lethal granuloma of the paranasal sinus and nasal cavity, stage II esthesioneuroblastoma of the paranasal sinus and nasal cavity, stage III squamous cell carcinoma of the paranasal sinus and nasal cavity, stage III inverted papilloma of the paranasal sinus and nasal cavity, stage III midline lethal granuloma of the paranasal sinus and nasal cavity, stage III esthesioneuroblastoma of the paranasal sinus and nasal cavity, stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity, stage IV inverted papilloma of the paranasal sinus and nasal cavity, stage IV midline lethal granuloma of the paranasal sinus and nasal cavity, stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent inverted papilloma of the paranasal sinus and nasal cavity, recurrent midline lethal granuloma of the paranasal sinus and nasal cavity, recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity, radiation toxicity