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

NCT ID: NCT00656513

Last Updated: 2019-11-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

196 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-09-30

Study Completion Date

2014-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Head and Neck Cancer Xerostomia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

One arm Phase II followed by a two-arm Phase III
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Pilocarpine: Phase III

Group Type ACTIVE_COMPARATOR

Pilocarpine

Intervention Type DRUG

5mg by mouth 3 times a day for 12 weeks

ALTENS: Phase III

Group Type EXPERIMENTAL

ALTENS

Intervention Type PROCEDURE

Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit

ALTENS: Phase II

Group Type EXPERIMENTAL

ALTENS

Intervention Type PROCEDURE

Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit

Interventions

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Pilocarpine

5mg by mouth 3 times a day for 12 weeks

Intervention Type DRUG

ALTENS

Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit

Intervention Type PROCEDURE

Other Intervention Names

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pilocarpine hydrochloride acupuncture-like transcutaneous electrical nerve stimulation

Eligibility Criteria

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Inclusion 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 Common Toxicity Criteria for Adverse Effects (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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

NRG Oncology

OTHER

Sponsor Role collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Raimond K. W. Wong, MD

Role: PRINCIPAL_INVESTIGATOR

Margaret and Charles Juravinski Cancer Centre

Locations

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UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Hospital of Saint Raphael

New Haven, Connecticut, United States

Site Status

Emory Crawford Long Hospital

Atlanta, Georgia, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

Saint Anthony's Hospital at Saint Anthony's Health Center

Alton, Illinois, United States

Site Status

Bloomington Hospital Regional Cancer Institute

Bloomington, Indiana, United States

Site Status

Center for Cancer Care at Goshen General Hospital

Goshen, Indiana, United States

Site Status

Methodist Cancer Center at Methodist Hospital

Indianapolis, Indiana, United States

Site Status

Boston University Cancer Research Center

Boston, Massachusetts, United States

Site Status

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Site Status

Schiffler Cancer Center at Wheeling Hospital

Wheeling, West Virginia, United States

Site Status

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

Site Status

Hopital Notre-Dame du CHUM

Montreal, Quebec, Canada

Site Status

McGill Cancer Centre at McGill University

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, Canada

Site Status

Countries

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United States Canada

References

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Wong RK, James JL, Sagar S, Wyatt G, Nguyen-Tan 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 Sep 1;118(17):4244-52. doi: 10.1002/cncr.27382. Epub 2012 Jan 17.

Reference Type RESULT
PMID: 22252927 (View on PubMed)

Related Links

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https://nctn-data-archive.nci.nih.gov/

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Other Identifiers

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CDR0000592644

Identifier Type: -

Identifier Source: secondary_id

RTOG-0537

Identifier Type: -

Identifier Source: org_study_id

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