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

Sponsors and Collaborators:	Radiation Therapy Oncology Group 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
Cancer-Related Problem/Condition Head and Neck Cancer	Drug: pilocarpine hydrochloride Procedure: acupuncture-like transcutaneous electrical nerve stimulation	Phase II Phase III

MedlinePlus related topics: Acupuncture Cancer Head and Neck Cancer

Drug Information available for: Pilocarpine Pilocarpine hydrochloride Pilocarpine nitrate

U.S. FDA Resources

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

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
Phase III, arm I: Active Comparator 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
Phase III, arm II: Experimental 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 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 at least 3 months prior to study entry
- Grade 1-2 radiotherapy-induced xerostomia according to the NCI CTCAE v.3.0 salivary gland changes/saliva xerostomia scale and the dry mouth/salivary gland xerostomia scale
- Must have evidence of residual salivary function with unstimulated whole salivary production of at least 0.25 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

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

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 2 weeks since prior pilocarpine and no concurrent use for ophthalmic or non-ophthalmic indications
No concurrent 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

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

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

Study ID Numbers:	CDR0000592644, RTOG-0537
Study First Received:	April 10, 2008
Last Updated:	October 31, 2008
ClinicalTrials.gov Identifier:	NCT00656513
Health Authority:	Unspecified

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

Study placed in the following topic categories:

Nasopharyngeal carcinoma
Metastatic squamous neck cancer with occult primary
Oral cancer
Head and Neck Neoplasms
Laryngeal carcinoma
Pilocarpine

Hypopharyngeal cancer
Laryngeal Neoplasms
Lip and oral cavity cancer
Salivary Gland Diseases
Xerostomia

Additional relevant MeSH terms:

Neurotransmitter Agents
Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Cholinergic Agonists
Autonomic Agents

Miotics
Physiological Effects of Drugs
Muscarinic Agonists
Peripheral Nervous System Agents
Cholinergic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009