Pilocarpine in Preventing Mucositis and Dry Mouth in Patients Receiving Radiation Therapy for Head and Neck Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as pilocarpine may protect normal cells from the side effects of radiation therapy. It is not yet known if pilocarpine may be effective in preventing mucositis and dry mouth in patients receiving radiation therapy for head and neck cancer. PURPOSE: Randomized, double-blinded, phase III trial to study the effectiveness of pilocarpine in preventing mucositis and dry mouth in patients receiving radiation therapy for head and neck cancer.

Detailed Description
-----------------
OBJECTIVES: I. Determine whether prophylactic use of pilocarpine can shelter unstimulated and stimulated whole salivary flow in patients with head and neck cancer. II. Determine whether prophylactic use of pilocarpine can moderate xerostomia in these patients. III. Determine whether prophylactic use of pilocarpine can reduce the grade and duration of radiation induced mucositis in these patients. IV. Evaluate quality of life outcomes between patients receiving pilocarpine versus placebo. V. Evaluate the impact of xerostomia on patients receiving irradiation to the head and neck. OUTLINE: This is a randomized, double blind study. Patients receive a central axis midplane dose of radiotherapy five days per week over 6 to 7 weeks. Oral pilocarpine or placebo is administered beginning 3 days prior to radiotherapy, one tablet four times per day for three months. A tablet will be taken 45-60 minutes before radiotherapy. After three months, and after a 3-4 day rest period, all patients receive non blinded pilocarpine for an additional three month period. Patients are followed at weeks 4, 13, and 26 after the start of radiotherapy. PROJECTED ACCRUAL: A total of 244 patients will be accrued (122 per treatment arm).

Official Title
-----------------
A Phase III Study to Test the Efficacy of the Prophylactic Use of Oral Pilocarpine to Reduce Hyposalivation and Mucositis Associated With Curative Radiation Therapy in Head and Neck Cancer Patients

Conditions
-----------------
Head and Neck Cancer, Oral Complications

Intervention / Treatment
-----------------
* Drug: pilocarpine hydrochloride
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically proven oral cavity and/or oropharyngeal squamous cell carcinoma Radiation volume to encompass at least 50% of parotid glands and have at least 50 Gy delivered to that volume via external beam No salivary gland malignancies or diseases PATIENT CHARACTERISTICS: Age: 18 and over Performance Status: Karnofsky 60-100% Life Expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Not pregnant or nursing Effective contraceptive method must be used during study No pilocarpine allergy PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to head or neck Surgery: Not specified Other: No concurrent adrenergic antagonists, cholinergic drugs, anti-cholinergics, or tricyclics

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pilocarpine hydrocloride<br>5mg pilocarpine hydrochloride tablets commencing 3 days prior to irradiation | Drug: pilocarpine hydrochloride<br>* 5mg pilocarpine hydrochloride tablets<br>|
| Placebo Comparator: Placebo<br>Placebo tablets commencing 3 days prior to irradiation | Other: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute salivary gland toxicity |  | From the start of treatment to 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute mucositis in the pharynx, palate, tongue, or buccal |  | From the start of treatment to 13 weeks | 
| Quality of life as measured by the University of Washington Head and Neck Symptom questionnaire |  | Pretreatment to 26 weeks from the start of treatment | 
| Effects of continuing pilocarpine out to 6 months from the start of treatment |  | From the start of treatment to 26 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
oral complications, lip and oral cavity squamous cell carcinoma, oropharyngeal squamous cell carcinoma