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.

Condition	Treatment or Intervention	Phase
Hypopharyngeal Cancer Laryngeal Cancer lip and oral cavity cancer metastatic squamous neck cancer with occult primary Nasopharyngeal Cancer oral complications of cancer and cancer therapy Oropharyngeal Cancer paranasal sinus and nasal cavity cancer radiation toxicity Salivary Gland Cancer	Drug: cevimeline  Procedure: complications of therapy assessment/management  Procedure: radioprotection  Procedure: supportive care/therapy	Phase III

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Alabama
      Mobile Infirmary Medical Center, Mobile,  Alabama,  36607,  United States; Recruiting
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States; Recruiting
Arizona
      Cranial Pain Research, Tucson,  Arizona,  85711,  United States; Recruiting
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205-7199,  United States; Recruiting
California
      Alta Bates Comprehensive Cancer Center, Berkeley,  California,  94704,  United States; Recruiting
      Chao Family Comprehensive Cancer Center, Orange,  California,  92868,  United States; Recruiting
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States; Recruiting
      Radiation Oncology Center - Sacramento, Sacramento,  California,  95816,  United States; Recruiting
      Rebecca and John Moores UCSD Cancer Center, San Diego,  California,  92103-8757,  United States; Recruiting
      Stanford University Medical Center, Stanford,  California,  94305-5408,  United States; Recruiting
Colorado
      Colorado Otolaryngology Associates, Colorado Springs,  Colorado,  80909,  United States; Recruiting
Connecticut
      University of Connecticut Health Center, Farmington,  Connecticut,  06360-7106,  United States; Recruiting
District of Columbia
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5000,  United States; Recruiting
Florida
      Innovative Medical Research of South Florida, Inc., Miami,  Florida,  33138,  United States; Recruiting
Georgia
      Medical College of Georgia Hospital and Clinics, Augusta,  Georgia,  30912,  United States; Recruiting
Idaho
      Kootenai Medical Center, Coeur D Alene,  Idaho,  83814,  United States; Recruiting
Illinois
      Evanston Northwestern Health Care, Evanston,  Illinois,  60201,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
      University of Illinois at Chicago, Chicago,  Illinois,  60612-7317,  United States; Recruiting
Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7321,  United States; Recruiting
Kentucky
      Louisville,  Kentucky,  40207,  United States; Recruiting
      Central Baptist Hospital, Lexington,  Kentucky,  40503,  United States; Recruiting
      James Graham Brown Cancer Center, Louisville,  Kentucky,  40202-3267,  United States; Recruiting
Louisiana
      Tulane Cancer Center, New Orleans,  Louisiana,  70112-2699,  United States; Recruiting
Maryland
      Harbor Hospital Center, Baltimore,  Maryland,  21215-1290,  United States; Recruiting
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21287-0910,  United States; Recruiting
Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States; Recruiting
Minnesota
      Ear, Nose, and Throat Specialty Care of Minnesota, P.A., Minneapolis,  Minnesota,  55404,  United States; Recruiting
      University of Minnesota School of Dentistry, Minneapolis,  Minnesota,  55455,  United States; Recruiting
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States; Recruiting
Missouri
      Siteman Cancer Center, Saint Louis,  Missouri,  63110-1093,  United States; Recruiting
      University of Missouri, Columbia,  Missouri,  65212,  United States; Recruiting
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-1225,  United States; Recruiting
      University of Nebraska Medical Center, Lincoln,  Nebraska,  68583,  United States; Recruiting
New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756-0002,  United States; Recruiting
New Jersey
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States; Recruiting
      Monmouth Medical Center, Long Branch,  New Jersey,  07740-6395,  United States; Recruiting
      Professional Otolaryngology Associates, Voorhees,  New Jersey,  08043,  United States; Recruiting
New York
      Albert Einstein Clinical Cancer Center, Bronx,  New York,  10461,  United States; Recruiting
      James P. Wilmot Cancer Center, Rochester,  New York,  14642,  United States; Recruiting
      Mount Sinai Medical Center, NY, New York,  New York,  10029,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      NYU - David B. Kriser Dental Center, New York,  New York,  10010-4086,  United States; Recruiting
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States; Recruiting
      State University of New York at Stony Brook School of Medicine, Stony Brook,  New York,  11794-8706,  United States; Recruiting
North Carolina
      Clinical Research of Winston Salem, Winston Salem,  North Carolina,  27103,  United States; Recruiting
      Comprehensive Cancer Center at Gaston Memorial, Gastonia,  North Carolina,  28053-1747,  United States; Recruiting
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
      Matthews Radiation Oncology Center, Matthews,  North Carolina,  28105,  United States; Recruiting
Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States; Recruiting
Oregon
      Oregon Cancer Institute, Portland,  Oregon,  97239,  United States; Recruiting
Pennsylvania
      Associated Otolaryngologist, Palmyra,  Pennsylvania,  17078,  United States; Recruiting
      Eye and Ear Institute, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
      Geisinger Medical Center, Danville,  Pennsylvania,  17822-1333,  United States; Recruiting
      Head and Neck Associates, Havertown,  Pennsylvania,  19083,  United States; Recruiting
      Kimmel Cancer Center of Thomas Jefferson University - Philadelphia, Philadelphia,  Pennsylvania,  19107-5541,  United States; Recruiting
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104-4283,  United States; Recruiting
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425,  United States; Recruiting
Tennessee
      Dial Research Associates, Inc., Nashville,  Tennessee,  37205,  United States; Recruiting
      Memorial Hospital Cancer Center - Chattanooga, Chattanooga,  Tennessee,  37404,  United States; Recruiting
      MultiSpecialty Clinical Research, Johnson City,  Tennessee,  37601,  United States; Recruiting
      Vanderbilt-Ingram Cancer Center, Nashville,  Tennessee,  37232-5671,  United States; Recruiting
Texas
      Baylor College of Dentistry, Dallas,  Texas,  75246,  United States; Recruiting
      Cancer Physicians Associates, PA, Laredo,  Texas,  78041,  United States; Recruiting
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States; Recruiting
Utah
      Latter Day Saints Hospital, Salt Lake City,  Utah,  84143,  United States; Recruiting
Virginia
      McLean,  Virginia,  22101,  United States; Recruiting
Washington
      Madigan Army Medical Center, Tacoma,  Washington,  98431,  United States; Recruiting
      Seattle Institute for Biomedical and Clinical Research, Seattle,  Washington,  98108,  United States; Recruiting
      Southwest Washington Medical Center, Vancouver,  Washington,  98664,  United States; Recruiting

Study chairs or principal investigators

Robert Vitti, MD,  Study Chair,  Daiichi Pharmaceuticals   

Study ID Numbers:  CDR0000068698; DAIICHI-2011A-PRT003/004; UCLA-0104045
Record last reviewed:  July 2001
Record first received:  June 6, 2001
ClinicalTrials.gov Identifier:  NCT00017511
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-10