Pilocarpine in Preventing Mucositis and Dry Mouth in Patients Receiving Radiation Therapy for Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

A Phase III Study to Test the Efficacy of the Prophylactic Use of Oral Pilocarpine to Reduce Hyposalivation and Mucositis Associated With Curative Radiation Therapy in Head and Neck Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003139
• Other study ID #: RTOG-9709
• Secondary ID: CDR0000065912NCI
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: November 14, 2015
• Start date: March 1998
• Est. completion date: October 2002

Study information

• Verified date: November 2015
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as pilocarpine may protect normal cells from the side effects of radiation therapy. It is not yet known if pilocarpine may be effective in preventing mucositis and dry mouth in patients receiving radiation therapy for head and neck cancer.

PURPOSE: Randomized, double-blinded, phase III trial to study the effectiveness of pilocarpine in preventing mucositis and dry mouth in patients receiving radiation therapy for head and neck cancer.

Description:

OBJECTIVES: I. Determine whether prophylactic use of pilocarpine can shelter unstimulated and stimulated whole salivary flow in patients with head and neck cancer. II. Determine whether prophylactic use of pilocarpine can moderate xerostomia in these patients. III. Determine whether prophylactic use of pilocarpine can reduce the grade and duration of radiation induced mucositis in these patients. IV. Evaluate quality of life outcomes between patients receiving pilocarpine versus placebo. V. Evaluate the impact of xerostomia on patients receiving irradiation to the head and neck.

OUTLINE: This is a randomized, double blind study. Patients receive a central axis midplane dose of radiotherapy five days per week over 6 to 7 weeks. Oral pilocarpine or placebo is administered beginning 3 days prior to radiotherapy, one tablet four times per day for three months. A tablet will be taken 45-60 minutes before radiotherapy. After three months, and after a 3-4 day rest period, all patients receive non blinded pilocarpine for an additional three month period. Patients are followed at weeks 4, 13, and 26 after the start of radiotherapy.

PROJECTED ACCRUAL: A total of 244 patients will be accrued (122 per treatment arm).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 249
• Est. completion date: October 2002
• Est. primary completion date: January 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS: Histologically proven oral cavity and/or oropharyngeal squamous cell carcinoma Radiation volume to encompass at least 50% of parotid glands and have at least 50 Gy delivered to that volume via external beam No salivary gland malignancies or diseases

PATIENT CHARACTERISTICS: Age: 18 and over Performance Status: Karnofsky 60-100% Life Expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Not pregnant or nursing Effective contraceptive method must be used during study No pilocarpine allergy

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to head or neck Surgery: Not specified Other: No concurrent adrenergic antagonists, cholinergic drugs, anti-cholinergics, or tricyclics

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms
• Oral Complications

Intervention

Drug:
• pilocarpine hydrochloride
5mg pilocarpine hydrochloride tablets

Other:
• Placebo

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Center - Calgary	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Cancer Care Ontario-Hamilton Regional Cancer Centre	Hamilton	Ontario
Canada	Kingston Regional Cancer Centre	Kingston	Ontario
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	Doctor Leon Richard Oncology Centre	Moncton	New Brunswick
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	Ottawa Regional Cancer Centre - Civic Campus	Ottawa	Ontario
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Northeastern Ontario Regional Cancer Centre, Sudbury	Sudbury	Ontario
Canada	Northwestern Ontario Regional Cancer Centre, Thunder Bay	Thunder Bay	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	British Columbia Cancer Agency - Vancouver Island Cancer Centre	Victoria	British Columbia
United States	Akron City Hospital	Akron	Ohio
United States	Akron General Medical Center	Akron	Ohio
United States	Cancer Center of Albany Medical Center	Albany	New York
United States	Veterans Affairs Medical Center - Albany	Albany	New York
United States	Saint Joseph Medical Center	Albuquerque	New Mexico
United States	Providence Cancer Therapy Center	Anchorage	Alaska
United States	St. John's Medical Center	Anderson	Indiana
United States	CCOP - Ann Arbor Regional	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan
United States	Anne Arundel Oncology Center	Annapolis	Maryland
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Greater Baltimore Medical Center and Cancer Center	Baltimore	Maryland
United States	Harbor Hospital Center	Baltimore	Maryland
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Radiation Oncology Affiliates of Maryland, P.A.	Baltimore	Maryland
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Julie and Ben Rogers Cancer Institute	Beaumont	Texas
United States	CCOP - Southwestern Vermont Regional Cancer Center	Bennington	Vermont
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama
United States	Veterans Affairs Medical Center - Birmingham	Birmingham	Alabama
United States	Joint Center for Radiation Therapy	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Medical Center at Bowling Green	Bowling Green	Kentucky
United States	Bridgeport Hospital	Bridgeport	Connecticut
United States	Albert Einstein Comprehensive Cancer Center	Bronx	New York
United States	New York Methodist Hospital	Brooklyn	New York
United States	State University of New York Health Science Center at Brooklyn	Brooklyn	New York
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cancer Center, University of Virginia HSC	Charlottesville	Virginia
United States	Martha Jefferson Hospital	Charlottesville	Virginia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Christ Hospital	Cincinnati	Ohio
United States	Lykes Center for Radiation Therapy	Clearwater	Florida
United States	Ireland Cancer Center	Cleveland	Ohio
United States	Memorial Hospital Cancer Center	Colorado Springs	Colorado
United States	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Mount Diablo Medical Center	Concord	California
United States	Samaritan Regional Cancer Center	Corvallis	Oregon
United States	Penn State Geisinger Medical Center	Danville	Pennsylvania
United States	Mercy Catholic Medical Center, Mercy Fitzgerald Divison	Darby	Pennsylvania
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Halifax Medical Center	Daytona Beach	Florida
United States	University of Colorado Cancer Center	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	Beckman Research Institute, City of Hope	Duarte	California
United States	Wendt Regional Cancer Center of Finley Hospital	Dubuque	Iowa
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	John F. Kennedy Medical Center	Edison	New Jersey
United States	Elizabeth General Medical Center - West	Elizabeth	New Jersey
United States	Meritcare Roger Maris Cancer Center	Fargo	North Dakota
United States	Hurley Medical Center	Flint	Michigan
United States	Radiation Therapy Associates - Fort Myers	Fort Myers	Florida
United States	California Cancer Center	Fresno	California
United States	Saint Agnes Cancer Center	Fresno	California
United States	University of Florida Health Science Center	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Glendale Memorial Hospital and Health Center	Glendale	California
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Sutter Health Western Division Cancer Research Group	Greenbrae	California
United States	CCOP - Greenville	Greenville	South Carolina
United States	East Carolina University School of Medicine	Greenville	North Carolina
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Penn State Geisinger Cancer Center	Hershey	Pennsylvania
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Huntsville Hospital System	Huntsville	Alabama
United States	Cape Cod Hospital	Hyannis	Massachusetts
United States	Clarion Health Partners Inc.	Indianapolis	Indiana
United States	Community Hospitals of Indianapolis - Regional Cancer Center	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Jackson-Madison County General Hospital	Jackson	Tennessee
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	CCOP - Dayton	Kettering	Ohio
United States	Baptist Regional Cancer Center - Knoxville	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Foundation	La Crosse	Wisconsin
United States	Wilford Hall - 59th Medical Wing	Lackland Air Force Base	Texas
United States	Romagosa Radiation Oncology Center	Lafayette	Louisiana
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Veterans Affairs Medical Center - Long Beach	Long Beach	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	Kaiser Permanente Medical Center - Los Angeles	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	Louisville Radiation Oncology	Louisville	Kentucky
United States	Virginia Baptist Hospital	Lynchburg	Virginia
United States	Southern Wisconsin Radiotherapy Center	Madison	Wisconsin
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Veterans Affairs Medical Center - Madison	Madison	Wisconsin
United States	Merle M. Mahr Cancer Center	Madisonville	Kentucky
United States	Elliot Regional Cancer Center	Manchester	New Hampshire
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	Marquette General Hospital	Marquette	Michigan
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Health First Holmes Regional Medical Center	Melbourne	Florida
United States	CCOP - Baptist Cancer Institute	Memphis	Tennessee
United States	University of Tennessee, Memphis Cancer Center	Memphis	Tennessee
United States	Community Memorial Hospital	Menomonee Falls	Wisconsin
United States	East Jefferson General Hospital	Metairie	Louisiana
United States	Baptist Hospital of Miami	Miami	Florida
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	South Jersey Hospital - Millville	Millville	New Jersey
United States	Columbia Hospital	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	St. Joseph's Hospital	Milwaukee	Wisconsin
United States	St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin
United States	UNI-MED Medical Center	Minot	North Dakota
United States	MBCCOP - University of South Alabama	Mobile	Alabama
United States	Urology Associates - Mobile AL	Mobile	Alabama
United States	Alabama Oncology, LLC	Montgomery	Alabama
United States	Fox Chase Cancer Center at Virtua-Memorial Hospital Burlington County	Mount Holly	New Jersey
United States	Ball Memorial Hospital	Muncie	Indiana
United States	Vanderbilt Cancer Center	Nashville	Tennessee
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Medical Center	New Orleans	Louisiana
United States	Kaplan Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Whittingham Cancer Center	Norwalk	Connecticut
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Methodist Cancer Center - Omaha	Omaha	Nebraska
United States	Florida Radiation Oncology Group	Orange Park	Florida
United States	MD Anderson Cancer Center Orlando	Orlando	Florida
United States	Western Baptist Hospital	Paducah	Kentucky
United States	Gulf Coast Cancer Treatment Center	Panama City	Florida
United States	Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	Bayshore Medical Center	Pasadena	Texas
United States	West Florida Cancer Institute - Pensacola	Pensacola	Florida
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Allegheny University Hospitals- Hahnemann	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center of Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	Veterans Affairs Medical Center - Philadelphia	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Champlain Valley Physicians Hospital Medical Center	Plattsburgh	New York
United States	Cancer Care Center	Pomona	California
United States	CCOP - Columbia River Program	Portland	Oregon
United States	Maine Medical Center	Portland	Maine
United States	Naval Medical Center, Portsmouth	Portsmouth	Virginia
United States	Vassar Brothers Hospital	Poughkeepsie	New York
United States	Southeastern Wisconsin Regional Cancer Center	Racine	Wisconsin
United States	Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Mercy Medical Center - Redding	Redding	California
United States	Massey Cancer Center	Richmond	Virginia
United States	Genesee Hospital - Rochester	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	University of Rochester Cancer Center	Rochester	New York
United States	InterCommunity Cancer Center at Rome	Rome	Georgia
United States	Green Mountain Oncology Group	Rutland	Vermont
United States	Radiation Oncology Center - Sacramento	Sacramento	California
United States	St. Mary's Medical Center	Saginaw	Michigan
United States	Dixie Regional Medical Center	Saint George	Utah
United States	Mallinckrodt Institute of Radiology	Saint Louis	Missouri
United States	St. Louis University Health Sciences Center	Saint Louis	Missouri
United States	Veterans Affairs Medical Center - Saint Louis	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Bayfront Medical Center	Saint Petersburg	Florida
United States	LDS Hospital	Salt Lake City	Utah
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Santa Cruz Radiation Oncology Medical Group, Inc.	Santa Cruz	California
United States	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania
United States	Swedish Hospital Tumor Institute	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Grand View Hospital	Sellersville	Pennsylvania
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	St. Joseph's Radiation Oncology Center	South Bend	Indiana
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Deaconess Medical Center	Spokane	Washington
United States	Cancer Research for the Ozarks	Springfield	Missouri
United States	CCOP - Central Illinois	Springfield	Illinois
United States	CCOP - Ozarks Regional	Springfield	Missouri
United States	Stanford University	Stanford	California
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	CCOP - Toledo Community Hospital Oncology Program	Toledo	Ohio
United States	Community Medical Center	Toms River	New Jersey
United States	David Grant Medical Center	Travis Air Force Base	California
United States	St. Francis Medical Center	Trenton	New Jersey
United States	Arizona Cancer Center	Tucson	Arizona
United States	St. John Medical Center	Tulsa	Oklahoma
United States	Radiation Oncology Associates of West Alabama	Tuscallosa	Alabama
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	South Georgia Medical Center	Valdosta	Georgia
United States	New York Medical College	Valhalla	New York
United States	Radiation Oncology Center - Walnut Creek	Walnut Creek	California
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Schiffler Oncology Center	Wheeling	West Virginia
United States	Veterans Affairs Medical Center - White River Junction	White River Junction	Vermont
United States	Wilkes Barre General Hospital	Wilkes-Barre	Pennsylvania
United States	CCOP - Christiana Care Health Services	Wilmington	Delaware
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Yakima Valley Memorial Hospital	Yakima	Washington
United States	York Hospital	York	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

Fisher J, Scott C, Scarantino CW, Leveque FG, White RL, Rotman M, Hodson DI, Meredith RF, Foote R, Bachman DG, Lee N. Phase III quality-of-life study results: impact on patients' quality of life to reducing xerostomia after radiotherapy for head-and-neck — View Citation

Fisher JJ, Scott CB, Scarantino CW, et al.: Phase III quality of life (Qol) study: reduction in hyposalivation does not improve Qol for head and neck (H&N) cancer patients post radiation therapy (P-RT). RTOG 9709. [Abstract] Proceedings of the American So

Scarantino C, LeVeque F, Swann RS, White R, Schulsinger A, Hodson DI, Meredith R, Foote R, Brachman D, Lee N. Effect of pilocarpine during radiation therapy: results of RTOG 97-09, a phase III randomized study in head and neck cancer patients. J Support O — View Citation

Scarantino CW, Leveque F, Scott C, et al.: A phase III study on the concurrent use of oral pilocarpine to reduce hyposalivation and mucositis associated with radiation therapy in head and neck cancer patients: final results of RTOG 97-09. [Abstract] Int J

Scarantino CW, Leveque FG, Scott CB, et al.: A phase III study of concomitant oral pilocarpine to reduce hypo-salivation and mucositis associated with curative radiation therapy (RT) in the head and neck (H&N) cancer patients. RTOG 9709. [Abstract] Procee

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute salivary gland toxicity		From the start of treatment to 13 weeks	Yes
Secondary	Acute mucositis in the pharynx, palate, tongue, or buccal		From the start of treatment to 13 weeks	Yes
Secondary	Quality of life as measured by the University of Washington Head and Neck Symptom questionnaire		Pretreatment to 26 weeks from the start of treatment	No
Secondary	Effects of continuing pilocarpine out to 6 months from the start of treatment		From the start of treatment to 26 weeks	Yes