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
Phase 3
18 Years
N/A
18 Years
N/A
Not Enrolling
Both
Head and Neck Cancer, Oral Complications, Radiation Toxicity
Both
Head and Neck Cancer, Oral Complications, Radiation Toxicity
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Supportive Care
Principal Investigator
Robert Vitti, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Daiichi Sankyo Inc.
Authority:
United States: Federal Government
Study ID:
CDR0000068698
NCT ID:
NCT00017511
Start Date:
June 2001
Completion Date:
March 2003
Related Keywords:
- Head and Neck Cancer
- Oral Complications
- Radiation Toxicity
- 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
- Head and Neck Neoplasms
- Radiation Injuries
Name | Location |
|---|---|
| University of Texas - MD Anderson Cancer Center | Houston, Texas 77030-4009 |
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
| Chao Family Comprehensive Cancer Center | Orange, California 92868 |
| Stanford University Medical Center | Stanford, California 94305-5408 |
| Walter Reed Army Medical Center | Washington, District of Columbia 20307-5000 |
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Kimmel Cancer Center of Thomas Jefferson University - Philadelphia | Philadelphia, Pennsylvania 19107 |
| University of Pennsylvania Cancer Center | Philadelphia, Pennsylvania 19104 |
| Medical University of South Carolina | Charleston, South Carolina 29425-0721 |
| Norris Cotton Cancer Center | Lebanon, New Hampshire 03756 |
| State University of New York - Upstate Medical University | Syracuse, New York 13210 |
| Mount Sinai Medical Center, NY | New York, New York 10029 |
| Geisinger Medical Center | Danville, Pennsylvania 17822-0001 |
| Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
| University of Alabama at Birmingham Comprehensive Cancer Center | Birmingham, Alabama 35294-3300 |
| Radiation Oncology Center - Sacramento | Sacramento, California 95816 |
| James Graham Brown Cancer Center | Louisville, Kentucky 40202 |
| Harbor Hospital Center | Baltimore, Maryland 21225 |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| Evanston Northwestern Health Care | Evanston, Illinois 60201 |
| North Shore University Hospital | Manhasset, New York 11030 |
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
| University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
| Madigan Army Medical Center | Tacoma, Washington 98431-5048 |
| Monmouth Medical Center | Long Branch, New Jersey 07740-6395 |
| University of Missouri | Columbia, Missouri 65212 |
| University of Nebraska Medical Center | Omaha, Nebraska 68198-3330 |
| Hackensack University Medical Center | Hackensack, New Jersey 07601 |
| Rebecca and John Moores UCSD Cancer Center | La Jolla, California 92093-0658 |
| James P. Wilmot Cancer Center | Rochester, New York 14642 |
| Albert Einstein Clinical Cancer Center | Bronx, New York 10461 |
| Oregon Cancer Institute | Portland, Oregon 97201-3098 |
| Mobile Infirmary Medical Center | Mobile, Alabama 36640-0460 |
| University of Connecticut Health Center | Farmington, Connecticut 06360-7106 |
| University of Illinois at Chicago | Chicago, Illinois 60612 |
| Central Baptist Hospital | Lexington, Kentucky 40503 |
| Latter Day Saints Hospital | Salt Lake City, Utah 84143 |
| Medical College of Georgia Hospital and Clinics | Augusta, Georgia 30912-3620 |
| Alta Bates Comprehensive Cancer Center | Berkeley, California 94704 |
| Tulane Cancer Center | New Orleans, Louisiana 70112 |
| Ear, Nose, and Throat Specialty Care of Minnesota, P.A. | Minneapolis, Minnesota 55404 |
| Siteman Cancer Center | Saint Louis, Missouri 63110 |
| Dial Research Associates, Inc. | Nashville, Tennessee 37205 |
| Memorial Hospital Cancer Center - Chattanooga | Chattanooga, Tennessee 37404 |
| Cranial Pain Research | Tucson, Arizona 85711 |
| Colorado Otolaryngology Associates | Colorado Springs, Colorado 80909 |
| Innovative Medical Research of South Florida, Inc. | Miami, Florida 33138 |
| Kootenai Medical Center | Coeur d'Alene, Idaho 83814 |
| Louisville, Kentucky 40207 | |
| University of Minnesota School of Dentistry | Minneapolis, Minnesota 55455 |
| Professional Otolaryngology Associates | Voorhees, New Jersey 08043 |
| NYU - David B. Kriser Dental Center | New York, New York 10010-4086 |
| State University of New York at Stony Brook School of Medicine | Stony Brook, New York 11794-8706 |
| Comprehensive Cancer Center at Gaston Memorial | Gastonia, North Carolina 28053-1747 |
| Matthews Radiation Oncology Center | Matthews, North Carolina 28105 |
| Clinical Research of Winston Salem | Winston-Salem, North Carolina 27103 |
| Head and Neck Associates | Havertown, Pennsylvania 19083 |
| Associated Otolaryngologist | Palmyra, Pennsylvania 17078 |
| Eye and Ear Institute | Pittsburgh, Pennsylvania 15213 |
| MultiSpecialty Clinical Research | Johnson City, Tennessee 37601 |
| Baylor College of Dentistry | Dallas, Texas 75246 |
| Cancer Physicians Associates, PA | Laredo, Texas 78041 |
| McLean, Virginia 22101 | |
| Seattle Institute for Biomedical and Clinical Research | Seattle, Washington 98108 |
| Southwest Washington Medical Center | Vancouver, Washington 98664 |
