Clinical trial NCT00656513: Acupuncture-Like Transcutaneous Electrical Nerve Stimulation (ALTENS) or Pilocarpine in Treating Early Dry Mouth in Patients Undergoing Radiation Therapy for 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Head and Neck Cancer
Xerostomia
Keywords: 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
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2008-04-11
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: One arm Phase II followed by a two-arm Phase III
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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 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

Primary outcomes:
measure: Phase II: Treatment Compliance (Number of Compliant Patients)
timeFrame: Randomization to 12 weeks
measure: Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months
timeFrame: Baseline (randomization) and 9 months
Secondary outcomes:
measure: Phase II: Pecentage of Patients With Beneficial Treatment Response
timeFrame: Pre-treatment and 6 months from registration
measure: Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III)
timeFrame: Baseline, 4, 6, and 15 months from randomization
measure: Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
timeFrame: Baseline, 4, 6, 9 and 15 months from randomization
measure: Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
timeFrame: Baseline, 4, 6, 9 and 15 months from randomization
measure: Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
timeFrame: Pre-treatment to 4, 6, 9 and 15 months from randomization
measure: Quality of Life (QOL) as Measured by the University of Washington Head and Neck Questionnaire (UWHNSS) Phase III
timeFrame: Baseline and 9 months from randomization.
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Hospital of Saint Raphael
state: Connecticut
city: Atlanta
country: United States
facility: Emory Crawford Long Hospital
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Alton
country: United States
facility: Saint Anthony's Hospital at Saint Anthony's Health Center
state: Illinois
city: Bloomington
country: United States
facility: Bloomington Hospital Regional Cancer Institute
state: Indiana
city: Goshen
country: United States
facility: Center for Cancer Care at Goshen General Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Cancer Center at Methodist Hospital
state: Indiana
city: Boston
country: United States
facility: Boston University Cancer Research Center
state: Massachusetts
city: Saint Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Wheeling
country: United States
facility: Schiffler Cancer Center at Wheeling Hospital
state: West Virginia
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital Notre-Dame du CHUM
state: Quebec
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
Study officials:
affiliation: Margaret and Charles Juravinski Cancer Centre
name: Raimond K. W. Wong, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.