Acupuncture-Like Transcutaneous Electrical Nerve Stimulation (ALTENS) or Pilocarpine in Treating Early Dry Mouth in Patients Undergoing Radiation Therapy for Head and Neck Cancer - Full Text View

Sponsor:	Radiation Therapy Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00656513

Purpose

RATIONALE: Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) and pilocarpine may help to relieve chronic xerostomia (dry mouth). It is not yet known which remedy is more effective in treating chronic dry mouth caused by radiation therapy in patients with head and neck cancer.

PURPOSE: This randomized phase II/III trial is studying ALTENS to see how well it works compared with pilocarpine in treating chronic dry mouth caused by radiation therapy in patients with head and neck cancer.

Condition	Intervention	Phase
Head and Neck Cancer Xerostomia	Drug: pilocarpine hydrochloride Procedure: acupuncture-like transcutaneous electrical nerve stimulation	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Supportive Care
Official Title:	A Phase II/III Study Comparing Acupuncture-like Transcutaneous Electrical Nerve Stimulation (ALTENS) Versus Pilocarpine in Treating Early Radiation-Induced Xerostomia

Resource links provided by NLM:

MedlinePlus related topics: Acupuncture Acute Bronchitis Cancer Dry Mouth Head and Neck Cancer

Drug Information available for: Pilocarpine hydrochloride Pilocarpine Pilocarpine nitrate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Successful delivery of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) treatment using the Codetron™ unit (phase II) [ Designated as safety issue: No ]
Overall xerostomia burden at 9 months after randomization, as measured by the University of Michigan 15-item Xerostomia Related Quality of Life Scale (XeQOLS) (phase III) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Beneficial treatment response, defined as a 20% improvement in overall xerostomia burden (XeQOLS score) from baseline to 6 months after study entry (phase II) [ Designated as safety issue: No ]
Overall xerostomia burden at 4, 6 and 15 months after randomization as measured by the XeQOLS (phase III) [ Designated as safety issue: No ]
Symptom burden at 4, 6, 9, and 15 months after randomization, as measured by the four domains of the XeQOLS: physical functioning, social functioning, personal/psychological functioning, and pain/discomfort (phase III) [ Designated as safety issue: No ]
Stimulated (i.e., citric acid primed) whole salivary production (WSP), as measured by sialometry at 4, 6, 9, and 15 months after randomization (phase III) [ Designated as safety issue: No ]
Unstimulated (i.e., basal primed) WSP as measured by sialometry at 4, 6, 9, and 15 months after randomization (phase III) [ Designated as safety issue: No ]
Adverse events as assessed by NCI CTCAE v.3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment:	189
Study Start Date:	September 2008
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Phase III, arm I Patients receive oral pilocarpine three times daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity.	Drug: pilocarpine hydrochloride Given by mouth 3 times a day for up to 12 weeks
Experimental: Phase III, arm II Patients undergo ALTENS treatment using the Codetron™ unit twice weekly for up to 12 weeks in the absence of disease progression or unacceptable toxicity.	Procedure: acupuncture-like transcutaneous electrical nerve stimulation Given twice a week for up to 12 weeks

Detailed Description:

OBJECTIVES:

Primary

Determine the feasibility of successfully delivering acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) using the Codetron™ unit in a cooperative group setting in head and neck cancer patients with early radiotherapy-induced xerostomia. (phase II)
Compare the efficacy of ALTENS treatment vs pilocarpine hydrochloride in these patients in reducing overall xerostomia burden, as measured by the University of Michigan 15-item Xerostomia-Related Quality of Life Scale (XeQOLS) at 9 months after randomization. (phase III)

Secondary

Evaluate the effect of ALTENS treatment on overall xerostomia burden at 6 months after study entry in these patients. (phase II)
Compare the efficacy of these treatments in these patients in reducing overall xerostomia burden at 4, 6, and 15 months after randomization. (phase III)
Compare the efficacy of these treatments in these patients in reducing symptom burden, as measured by the four domains of the XeQOLS (i.e., physical functioning, social functioning, personal/psychological functioning, and pain/discomfort) at 4, 6, 9, and 15 months after randomization. (phase III)
Compare the efficacy of these treatments in these patients in increasing stimulated (i.e., citric acid primed) whole salivary production (WSP), as measured by sialometry, at 4, 6, 9, and 15 months after randomization. (phase III)
Compare the efficacy of these treatments in these patients in increasing unstimulated (i.e., basal primed) WSP, as measured by sialometry at 4, 6, 9, and 15 months after randomization. (phase III)
Compare adverse events associated with these treatments in these patients. (phase III)

OUTLINE: This is a phase II followed by a phase III multicenter study.

Phase II:Patients undergo placement of surface electrodes at the following acupuncture points: large intestine, spleen, stomach, and conception vessel. Patients then undergo acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) to each of these points using the Codetron™ unit for 20 minutes twice weekly for 12 weeks. No further treatment is given after 12 weeks.
Phase III:Patients are stratified according to prior use of pilocarpine (no vs yes) and length of time from completion of chemotherapy and/or radiotherapy (3-6 months vs 6-12 months vs > 12 months). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral pilocarpine three times daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients undergo ALTENS treatment using the Codetron™ unit twice weekly for up to 12 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo quality of life (QOL) assessment at baseline and at 6 months after registration in phase II. In phase III patients complete assessments for basal and stimulated whole salivary production, xerostomia burden, and QOL at baseline and at 4, 6, 9, and 15 months after study entry.

After completion of study therapy, patients are followed at 3 months.

PROJECTED ACCRUAL: A total of 45 patients will be accrued to the phase II portion and 144 patients to the phase III portion of this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of head and neck cancer
- No clinical evidence of disease recurrence by ear, nose, and throat exam with a nasopharyngeal scope, if indicated, 8 weeks prior to registration
Completed radiotherapy (i.e., standard or intensity-modulated radiotherapy) with or without chemotherapy ≥ 3 months and up to 2 years prior to study entry
- Grade 1-2 radiotherapy-induced xerostomia according to the NCI CTCAE v.3.0 and the dry mouth/salivary gland xerostomia scale
- Must have evidence of residual salivary function with unstimulated (basal) whole salivary production ≥ 0.1 ml/min after having refrained from eating or drinking oral fluid for 2 hours
No patients with normal saliva production (i.e., no salivary gland changes or no xerostomia)
No history of serious adverse events after prior treatment with and discontinuation of pilocarpine
No chronic lymphocytic leukemia

PATIENT CHARACTERISTICS:

See Disease Characteristics
Zubrod performance status of 0-2
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other invasive malignancy except non-melanomatous skin cancer or cancer from which the patient has been disease-free for at least 3 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix)
No concurrent contraindications to pilocarpine (e.g., uncontrolled asthma, miosis, or hypersensitivity)
No severe, active co-morbidity, including any of the following:
- Unstable cardiac disease or requirement for a pacemaker in-situ
- Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
- Transmural myocardial infarction within the past 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
No Sjögren syndrome

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 2 weeks since prior pilocarpine or cevimeline and no concurrent use for ophthalmic or non-ophthalmic indications
No concurrent regular medications that induce xerostomia (e.g., tricyclic antidepressants, antihistamines with anticholinergic effects, or narcotics)
No concurrent oral stimulating agents or salivary gland medical stimulants

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00656513

Locations

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Connecticut
Hospital of Saint Raphael
New Haven, Connecticut, United States, 06511
United States, Georgia
Emory Crawford Long Hospital
Atlanta, Georgia, United States, 30308
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Saint Anthony's Hospital at Saint Anthony's Health Center
Alton, Illinois, United States, 62002
United States, Indiana
Bloomington Hospital Regional Cancer Institute
Bloomington, Indiana, United States, 47403
Center for Cancer Care at Goshen General Hospital
Goshen, Indiana, United States, 46526
Methodist Cancer Center at Methodist Hospital
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Boston University Cancer Research Center
Boston, Massachusetts, United States, 02118
United States, Missouri
CCOP - St. Louis-Cape Girardeau
Saint Louis, Missouri, United States, 63141
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Oklahoma
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, West Virginia
Schiffler Cancer Center at Wheeling Hospital
Wheeling, West Virginia, United States, 26003
Canada, Quebec
Hopital Notre-Dame du CHUM
Montreal, Quebec, Canada, H2L 4M1
Maisonneuve-Rosemont Hospital
Montreal, Quebec, Canada, H1T 2M4
McGill Cancer Centre at McGill University
Montreal, Quebec, Canada, H2W 1S6
Centre Hospitalier Universitaire de Quebec
Quebec City, Quebec, Canada, G1R 2J6

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Raimond K. W. Wong, MD

Margaret and Charles Juravinski Cancer Centre

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Wong RK, James JL, Sagar S, Wyatt G, Nguyen-Tân PF, Singh AK, Lukaszczyk B, Cardinale F, Yeh AM, Berk L. Phase 2 results from Radiation Therapy Oncology Group Study 0537: A phase 2/3 study comparing acupuncture-like transcutaneous electrical nerve stimulation versus pilocarpine in treating early radiation-induced xerostomia. Cancer. 2012 Jan 17; [Epub ahead of print]

Responsible Party:	Walter John Curran, Jr, Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:	NCT00656513 History of Changes
Other Study ID Numbers:	CDR0000592644, RTOG-0537
Study First Received:	April 10, 2008
Last Updated:	January 27, 2012
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

hypopharyngeal cancer
laryngeal cancer
lip and oral cavity cancer
nasopharyngeal cancer
paranasal sinus and nasal cavity cancer

oropharyngeal cancer
salivary gland cancer
metastatic squamous neck cancer with occult primary
xerostomia
tongue cancer

Additional relevant MeSH terms:

Head and Neck Neoplasms
Xerostomia
Neoplasms by Site
Neoplasms
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Pilocarpine
Miotics

Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Muscarinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012