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An Investigator-Initiated,Multicenter,Randomized,Double-Blind Placebo-Controlled Design Study to Assess the Effectiveness of CeviMeline to Improve OraL Health in Patients With XErostomia Secondary to Radiation Therapy for Treatment of Head and Neck Squamous Cell Carcinoma

Phase 4
18 Years
Open (Enrolling)

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Trial Information

An Investigator-Initiated,Multicenter,Randomized,Double-Blind Placebo-Controlled Design Study to Assess the Effectiveness of CeviMeline to Improve OraL Health in Patients With XErostomia Secondary to Radiation Therapy for Treatment of Head and Neck Squamous Cell Carcinoma

Treatment of advanced head and neck squamous cell carcinoma (SCCA) requires aggressive
therapy often combining surgical interventions with radiation therapy. Besides surveillance
for persistent or recurrent cancer, clinicians seek to help minimize the side effects
resulting from these aggressive treatments. Xerostomia, or "dry mouth", impacts each
patient's long term health and quality of life due to the significant and diverse health
consequences of having too little saliva. Normal swallowing, speaking, resistance to
infection, and taste acuity are health domains that are affected by dry mouth. Psycho-social
functioning decreases for many of these patients due to the extra effort to communicate and
socialize (Locker D 2004).

Xerostomia is often a consequence of radiation treatment (XRT), especially when the XRT
fields encompass the parotid glands and submandibular glands bilaterally. The disability and
consequences of xerostomia extend beyond dysphagia, poor appetite secondary to difficulty of
mastication, and loss of taste (Chambers et al. Xerostomia 2004). Since saliva is essential
to normal oral flora and healthy teeth, the lack of saliva in these patients can
dramatically and rapidly result in a decline of the patient's oral health. Dental
complications can occur and present significant ongoing medical and surgical problems.

Our study proposes to use the Oral Health Impact Profile, OHIP-49, to measure
disease-specific quality of life and functional outcomes due to radiation related xerostomia
in head and neck cancer patients. The evaluation of patient QOL concomitantly with patient
functioning as proposed in the SMILE protocol is an "evidence study to evaluate treatment
effectiveness". The use of patient-oriented outcome measures are increasingly important to
health insurers and government, but these measures are also aligned with the World Health
Organization's mandate that health is a resource to manage which must be utilized and
preserved so that individuals experience and gain satisfaction from living (Epstein J.1986).
The OHIP-49 is patient reported outcome measure which is publicly available, validated in
adult populations world-wide, and can be used an effectiveness measure. The questions are
easy to answer and are based upon a 5 level likert type scale reflecting frequency of
"bother" within individual psychosocial domains.

Inclusion Criteria:

- Subject is at least 18 years old and able to give written informed consent

- Subject has received external beam radiotherapy > 4000 cGy for SCCA of the head
and/or neck

- Radiation therapy was completed at least 16 weeks (4 months) prior to enrollment into
the study but not greater than 52 weeks (12 months)

- Radiation included at least three of four of the major salivary glands (submandibular
and parotid glands) in the initial field (boost fields may or may not include the
parotid gland)

- Primary therapy was designed with curative intent. Surgery is permitted if the
remaining inclusion criteria are met

- Grade 1 or 2 xerostomia by CTC version 3.0 criteria (Appendix D)

- Demonstratable salivary flow as assessed by the clinician after administration of a
potent sialogogue such as lemon juice (1 teaspoon)

- Subject has at least one anatomically intact parotid gland and one submandibular

- ECOG performance status of 0, 1, or 2

- An EKG obtained has been performed in the past 6 months showing no arrhythmias or
contraindication to administration of a muscarinic agent AND there has been no
interval change in cardiac health

- Subject is able to eat an oral diet to maintain adequate hydration and nutrition

- Subject has provided informed consent

- Subject is English speaking and of sufficient mental capacity to comply with the
study requirements

- Female subjects of child bearing potential have a negative serum pregnancy test and
agree to use an approved method of birth control

Exclusion Criteria:

- Subject has a life expectancy less than 12 months.

- Subject is known or suspected to have persistent disease after curative intent

- Subject is greater than 12 months out from completion of radiation therapy

- Subject is pregnant or nursing

- Subject had previous cancer of the head and/or neck and is being treated with a
second course of radiation therapy

- Subject has a history of an autoimmune disease with pretreatment xerostomia (i.e.
Sjogrens) or other underlying systemic illness known to cause xerostomia independent
of prior radiation therapy exposure

- Subject has had resection of both parotid glands

- Subject has history of cardiomyopathy or untreated moderate to severe CAD

- Subject has known cardiac arrhythmias

- Subject has grade 3 xerostomia (CTC v.3)or no demonstratable salivary flow after the
test dose by visual inspection

- Subject has history of significant renal or hepatic impairment

- Subject uses a gastrostomy tube for nutrition supplementation

- Subject is taking medications specified in Appendix C

- Subject is taking or has taken any investigational new drug within the last 30 days
or is planning to take such a drug during the course of this study

- Subject has a contraindication to administration of muscarinic medications.

- Subject has been treated previously with a muscarinic agent for xerostomia (i.e.,
Pilocarpine HCl)

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Outcome Measure:

To assess the impact of increased salivary flow due to treatment with cevimeline compared to placebo in patient reported oral health using the OHIP-49

Principal Investigator

David Witsell, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Institutional Review Board

Study ID:




Start Date:

May 2007

Completion Date:

November 2008

Related Keywords:

  • Xerostomia
  • dry mouth
  • Carcinoma, Squamous Cell
  • Xerostomia



Carle Clinic Association Urbana, Illinois  61801
University of Kansas Medical Center Kansas City, Kansas  66160-7353
University of Pittsburgh Pittsburgh, Pennsylvania  15261
Associated Otolaryngologist Palmyra, Pennsylvania  17078
Denver, Colorado  
Commonwealth Ear, Nose and Throat Louisville, Kentucky  40207
Fauquier ENT Consultants Warrenton, Virginia  20186