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

Condition(s) targeted: Head and Neck Cancer; Xerostomia

Intervention: pilocarpine hydrochloride (Drug); acupuncture-like transcutaneous electrical nerve stimulation (Procedure)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: Radiation Therapy Oncology Group

Official(s) and/or principal investigator(s):
Raimond K. W. Wong, MD, Principal Investigator, Affiliation: Margaret and Charles Juravinski Cancer Centre

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.

Official title: A Phase II/III Study Comparing Acupuncture-like Transcutaneous Electrical Nerve Stimulation (ALTENS) Versus Pilocarpine in Treating Early Radiation-Induced Xerostomia

Study design: Supportive Care, Randomized

Primary outcome:

Successful delivery of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) treatment using the Codetron™ unit (phase II)

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)

Secondary outcome:

Beneficial treatment response, defined as a 20% improvement in overall xerostomia burden (XeQOLS score) from baseline to 6 months after study entry (phase II)

Overall xerostomia burden at 4, 6 and 15 months after randomization as measured by the XeQOLS (phase III)

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)

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)

Unstimulated (i.e., basal primed) WSP as measured by sialometry at 4, 6, 9, and 15 months after randomization (phase III)

Adverse events as assessed by NCI CTCAE v.3.0

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94115, United States; Recruiting
Clinical Trials Office - UCSF Helen Diller Family Comprehensi, Phone: 877-827-3222

Hospital of Saint Raphael, New Haven, Connecticut 06511, United States; Recruiting
Clinical Trials Office - Hospital of Saint Raphael, Phone: 203-789-3545

Good Samaritan Regional Health Center, Mt. Vernon, Illinois 62864, United States; Recruiting
Bethany G. Sleckman, MD, Phone: 314-251-7057

John H. Stroger, Jr. Hospital of Cook County, Chicago, Illinois 60612-3785, United States; Recruiting
Nathanial O. Holloway, Phone: 312-864-3200

Saint Anthony's Hospital at Saint Anthony's Health Center, Alton, Illinois 62002, United States; Recruiting
Bethany G. Sleckman, MD, Phone: 314-251-7057

Center for Cancer Care at Goshen General Hospital, Goshen, Indiana 46526, United States; Recruiting
Clinical Trials Office - Center for Cancer Care at Goshen Gene, Phone: 574-535-2858

Methodist Cancer Center at Methodist Hospital, Indianapolis, Indiana 46202, United States; Recruiting
Alexander M. Yeh, MD, Phone: 317-962-3172

Boston University Cancer Research Center, Boston, Massachusetts 02118, United States; Recruiting
Clinical Trials Office - Boston University Cancer Research Cen, Phone: 617-353-7571

Community Cancer Center of Monroe, Monroe, Michigan 48162, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

Haematology-Oncology Associates of Ohio and Michigan, PC, Lambertville, Michigan 48144, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

Hickman Cancer Center at Bixby Medical Center, Adrian, Michigan 49221, United States; Recruiting
Clinical Trials Office - Hickman Cancer Center at Bixby Medica, Phone: 517-265-0116

Mercy Memorial Hospital - Monroe, Monroe, Michigan 48162, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

CCOP - St. Louis-Cape Girardeau, Saint Louis, Missouri 63141, United States; Recruiting
Bethany G. Sleckman, MD, Phone: 314-251-7057

David C. Pratt Cancer Center at St. John's Mercy, Saint Louis, Missouri 63141, United States; Recruiting
Clinical Trials Office - David C. Pratt Cancer Center at St. J, Phone: 314-251-6770

Midwest Hematology Oncology Group, Incorporated, Saint Louis, Missouri 63109, United States; Recruiting
Bethany G. Sleckman, MD, Phone: 314-251-7057

Saint Francis Medical Center, Cape Girardeau, Missouri 63703, United States; Recruiting
Bethany G. Sleckman, MD, Phone: 314-251-7057

Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital, Cape Girardeau, Missouri 63701, United States; Recruiting
Bethany G. Sleckman, MD, Phone: 314-251-7057

Lipson Cancer and Blood Center at Rochester General Hospital, Rochester, New York 14621, United States; Recruiting
Meri Atanas, Phone: 585-922-4020

Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States; Recruiting
Clinical Trials Office - Roswell Park Cancer Institute, Phone: 877-275-7724

Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States; Recruiting
Clinical Trials Office - Blumenthal Cancer Center at Carolinas, Phone: 704-355-2884

CCOP - Toledo Community Hospital, Toledo, Ohio 43617, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

Flower Hospital Cancer Center, Sylvania, Ohio 43560, United States; Recruiting
Clinical Trials Office - Flower Hospital Cancer Center, Phone: 419-824-1842

Fulton County Health Center, Wauseon, Ohio 43567, United States; Recruiting
Clinical Trials Office - Fulton County Health Center, Phone: 419-330-2708

Hematology Oncology Center, Elyria, Ohio 44035, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

Lima Memorial Hospital, Lima, Ohio 45804, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

Medical University of Ohio Cancer Center, Toledo, Ohio 43614, United States; Recruiting
Clinical Trials Office - Medical University of Ohio Cancer Cen, Phone: 419-383-6583

Mercy Hospital of Tiffin, Tiffin, Ohio 44883, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

North Coast Cancer Care - Clyde, Clyde, Ohio 43410, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

North Coast Cancer Care, Incorporated, Sandusky, Ohio 44870, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

Northwest Ohio Oncology Center, Maumee, Ohio 43537-1839, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

St. Anne Mercy Hospital, Toledo, Ohio 43623, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

St. Charles Mercy Hospital, Oregon, Ohio 43616, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

St. Luke's Hospital, Maumee, Ohio 43537, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

St. Vincent Mercy Medical Center, Toledo, Ohio 43608, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

Toledo Clinic - Oregon, Oregon, Ohio 43616, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

Toledo Clinic, Incorporated - Main Clinic, Toledo, Ohio 43623, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

Toledo Hospital, Toledo, Ohio 43606, United States; Recruiting
Clinical Trials Office - Toledo Hospital, Phone: 419-824-1842

Wood County Oncology Center, Bowling Green, Ohio 43402, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

Oklahoma University Cancer Institute, Oklahoma City, Oklahoma 73104, United States; Recruiting
Terence S. Herman, Phone: 405-271-6822

Adventist Medical Center, Portland, Oregon 97216, United States; Recruiting
Matthew C. Solhjem, Phone: 503-257-2500

CCOP - Columbia River Oncology Program, Portland, Oregon 97225, United States; Recruiting
Matthew C. Solhjem, Phone: 503-216-6260

Providence Cancer Center at Providence Portland Medical Center, Portland, Oregon 97213-2967, United States; Recruiting
Clinical Trials Office - Providence Cancer Center at Providenc, Phone: 503-215-6412

Providence Milwaukie Hospital, Milwaukie, Oregon 97222, United States; Recruiting
Matthew C. Solhjem, Phone: 503-513-8300

Providence St. Vincent Medical Center, Portland, Oregon 97225, United States; Recruiting
Clinical Trials Office - Providence St. Vincent Medical Center, Phone: 503-215-6412

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia, Philadelphia, Pennsylvania 19107-5541, United States; Recruiting
Clinical Trials Office - Kimmel Cancer Center at Thomas Jeffer, Phone: 215-955-6084

St. Luke's Cancer Network at St. Luke's Hospital, Bethlehem, Pennsylvania 18015, United States; Recruiting
Nimisha Deb, MD, Phone: 610-954-4300

Centre Hospitalier Universitaire de Quebec, Quebec City, Quebec G1R 2J6, Canada; Recruiting
Chang S. Wang, Phone: 418-525-4444

Hopital Notre-Dame du CHUM, Montreal, Quebec H2L 4M1, Canada; Recruiting
Phuc Felix Nguyen-Tan, Phone: 514-281-6000

Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; Recruiting
Pierre Chabot, Phone: 514-252-3400

AnMed Cancer Center, Anderson, South Carolina 29621, United States; Recruiting
Clinical Trials Office - AnMed Cancer Center, Phone: 864-512-1000

CCOP - Upstate Carolina, Spartanburg, South Carolina 29303, United States; Recruiting
Clinical Trials Office - CCOP - Upstate Carolina, Phone: 800-486-5941

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center, Spartanburg, South Carolina 29303, United States; Recruiting
Clinical Trials Office - Gibbs Regional Cancer Center, Phone: 800-486-5941

Rapid City Regional Hospital, Rapid City, South Dakota 57701, United States; Recruiting
Eric S. Eastmo, MD, Phone: 605-719-2360

Fredericksburg Oncology, Incorporated, Fredericksburg, Virginia 22401, United States; Recruiting
Paul L. Schaefer, MD, Phone: 419-479-5605

University of Virginia Cancer Center, Charlottesville, Virginia 22908, United States; Recruiting
Paul W. Read, Phone: 434-924-9333

Southwest Washington Medical Center Cancer Center, Vancouver, Washington 98668, United States; Recruiting
Matthew C. Solhjem, Phone: 360-514-2174

Schiffler Cancer Center at Wheeling Hospital, Wheeling, West Virginia 26003, United States; Recruiting
Jon D. Pollock, MD, Phone: 304-243-3490

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: September 2008
Last updated: September 5, 2009