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

NCT00656513 | Completed Phase 2 Results DMC

• 2 other identifiers: RTOG-0537CDR0000592644
• Study Type: interventional
• Target: 196
• Locations: 2 countries
• Sites: 20

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.

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

Outcome Measures

Primary Outcomes (2)

• Phase II: Treatment Compliance (Number of Compliant Patients)

  Patients completing at least 19 out of 24 ALTENS therapy sessions were categorized as compliant. Fleming's two-stage was used, assuming a successful target compliance rate of 80%, statistical power of 0.87, and a type I error rate of 0.13. If fewer than 9 of the first 13 patients were compliant, then treatment delivery will be deemed not feasible. If there were between 9-12 compliant patients, the second stage analysis would be required to determine feasibility of treatment delivery. If all 13 patients are compliant, treatment delivery will immediately be deemed feasible. The second stage analysis required at least 31 compliant out of 39 overall patients for the treatment delivery to be deemed feasible.

  Randomization to 12 weeks

• Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months

  Xerostomia burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4, with higher scores indicating increased xerostomia burden. Change in xerostomia burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the xerostomia burden.

  Baseline (randomization) and 9 months

Secondary Outcomes (6)

• Phase II: Pecentage of Patients With Beneficial Treatment Response

  Pre-treatment and 6 months from registration

• Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III)

  Baseline, 4, 6, and 15 months from randomization

• Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)

  Baseline, 4, 6, 9 and 15 months from randomization

• Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)

  Baseline, 4, 6, 9 and 15 months from randomization

• Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)

  Pre-treatment to 4, 6, 9 and 15 months from randomization

Study Arms (3)

Pilocarpine: Phase III

ACTIVE COMPARATOR

Drug: Pilocarpine

ALTENS: Phase III

EXPERIMENTAL

Procedure: ALTENS

ALTENS: Phase II

EXPERIMENTAL

Procedure: ALTENS

Interventions

Pilocarpine DRUG

5mg by mouth 3 times a day for 12 weeks

Also known as: pilocarpine hydrochloride

Pilocarpine: Phase III

ALTENS PROCEDURE

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

Also known as: acupuncture-like transcutaneous electrical nerve stimulation

ALTENS: Phase II; ALTENS: Phase III

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• NRG Oncology: collaborator

Study Sites (20)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Hospital of Saint Raphael

New Haven, Connecticut, 06511, United States

Location

Emory Crawford Long Hospital

Atlanta, Georgia, 30308, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

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

Alton, Illinois, 62002, United States

Location

Bloomington Hospital Regional Cancer Institute

Bloomington, Indiana, 47403, United States

Location

Center for Cancer Care at Goshen General Hospital

Goshen, Indiana, 46526, United States

Location

Methodist Cancer Center at Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Boston University Cancer Research Center

Boston, Massachusetts, 02118, United States

Location

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, 63141, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, 28232-2861, United States

Location

Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Schiffler Cancer Center at Wheeling Hospital

Wheeling, West Virginia, 26003, United States

Location

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

Hopital Notre-Dame du CHUM

Montreal, Quebec, H2L 4M1, Canada

Location

McGill Cancer Centre at McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

Related Publications (1)

• 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.

  PMID: 22252927 RESULT

Related Links

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

MeSH Terms

Conditions

Head and Neck Neoplasms; Xerostomia; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Mouth Neoplasms; Nasopharyngeal Neoplasms; Oropharyngeal Neoplasms; Salivary Gland Neoplasms; Tongue Neoplasms

Interventions

Pilocarpine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Nasopharyngeal Diseases; Tongue Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Wendy Seiferheld, M.S.
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

Study Officials

• Raimond K. W. Wong, MD

  Margaret and Charles Juravinski Cancer Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: One arm Phase II followed by a two-arm Phase III

Study Record Dates

• First Submitted: April 10, 2008
• First Posted: April 11, 2008
• Study Start: September 1, 2008
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: November 19, 2019
• Results First Posted: August 21, 2017

Record last verified: 2017-07

Locations

CA (4); US (16)