Clinical trial NCT00017511: Cevimeline in Treating Patients With Dry Mouth Caused by Radiation Therapy for Head and Neck Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Head and Neck Cancer
Oral Complications
Radiation Toxicity
Keywords: 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
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Tucson
country: United States
facility: Cranial Pain Research
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Berkeley
country: United States
facility: Alta Bates Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: Radiation Oncology Center - Sacramento
state: California
city: San Diego
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Colorado Springs
country: United States
facility: Colorado Otolaryngology Associates
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Miami
country: United States
facility: Innovative Medical Research of South Florida, Inc.
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia Hospital and Clinics
state: Georgia
city: Coeur d'Alene
country: United States
facility: Kootenai Medical Center
state: Idaho
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Evanston
country: United States
facility: Evanston Northwestern Health Care
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Central Baptist Hospital
state: Kentucky
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: Harbor Hospital Center
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Minneapolis
country: United States
facility: Ear, Nose, and Throat Specialty Care of Minnesota, P.A.
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota School of Dentistry
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Lincoln
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Voorhees
country: United States
facility: Professional Otolaryngology Associates
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein Clinical Cancer Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: NYU - David B. Kriser Dental Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center, NY
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center
state: New York
city: Stony Brook
country: United States
facility: State University of New York at Stony Brook School of Medicine
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Gastonia
country: United States
facility: Comprehensive Cancer Center at Gaston Memorial
state: North Carolina
city: Matthews
country: United States
facility: Matthews Radiation Oncology Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Clinical Research of Winston Salem
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Cancer Institute
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Havertown
country: United States
facility: Head and Neck Associates
state: Pennsylvania
city: Palmyra
country: United States
facility: Associated Otolaryngologist
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Eye and Ear Institute
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Chattanooga
country: United States
facility: Memorial Hospital Cancer Center - Chattanooga
state: Tennessee
city: Johnson City
country: United States
facility: MultiSpecialty Clinical Research
state: Tennessee
city: Nashville
country: United States
facility: Dial Research Associates, Inc.
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor College of Dentistry
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Laredo
country: United States
facility: Cancer Physicians Associates, PA
state: Texas
city: Salt Lake City
country: United States
facility: Latter Day Saints Hospital
state: Utah
city: McLean
country: United States
state: Virginia
city: Seattle
country: United States
facility: Seattle Institute for Biomedical and Clinical Research
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Vancouver
country: United States
facility: Southwest Washington Medical Center
state: Washington
Study officials:
affiliation: Daiichi Sankyo
name: Robert Vitti, MD
role: STUDY_CHAIR
References: