Neoplasms

All Conditions

Mouth and Tooth Diseases

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Xerostomia

Mucositis

Gastroenteritis

Gastrointestinal Diseases

Mouth Diseases

Stomatognathic Diseases

Oral Squamous Cell Carcinoma

All Drugs and Chemicals

Pilocarpine

Muscarinic Agonists

Cholinergic Agents

Neurotransmitter Agents

5mg pilocarpine hydrochloride tablets commencing 3 days prior to irradiation

Placebo tablets commencing 3 days prior to irradiation

pilocarpine hydrochloride

Placebo

Francis G. LeVeque, DDS

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.

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).

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

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

National Cancer Institute (NCI)

Radiation Therapy Oncology Group

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Recurrence

Breast Diseases

Skin Diseases

Patients receive oral pilocarpine hydrochloride once a day for 3 days, twice a day for 3 days, three times a day for 3 days, and then 4 times a day for up to 6 weeks in the absence of unacceptable toxicity.

Patients receive oral pilocarpine hydrochloride once a day for 3 days and then twice a day for up to 6 weeks in the absence of unacceptable toxicity.

Patients receive oral placebo once a day for 3 days, twice a day for 3 days, three times a day for 3 days, and then 4 times a day for up to 6 weeks in the absence of unacceptable toxicity.

Patients receive oral placebo once a day for 3 days and then twice a day for up to 6 weeks in the absence of unacceptable toxicity.

placebo

Charles L. Loprinzi, MD

RATIONALE: Pilocarpine may decrease vaginal dryness and improve quality of life in patients with breast cancer It is not yet known whether pilocarpine is more effective than a placebo in treating vaginal dryness in patients with breast cancer.

PURPOSE: This randomized phase III trial is studying pilocarpine to see how well it works compared to a placebo in treating vaginal dryness in patients with breast cancer.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (18 to 45 vs 46 to 55 vs 56 to 65 vs \> 65), concurrent tamoxifen therapy (yes vs no vs unknown \[e.g., on a blinded clinical study\]), concurrent aromatase inhibitor therapy (yes vs no vs unknown \[e.g., on a blinded clinical study\]), and perception of severity of vaginal symptoms at baseline (mild vs moderate vs severe). Patients are randomized to 1 of 4 treatment arms. The primary and secondary objectives of the study are described below.

OBJECTIVES:

Primary

* Determine the effectiveness of pilocarpine hydrochloride for alleviation of vaginal dryness in patients with breast cancer.

Secondary

* Evaluate any toxicities arising from pilocarpine hydrochloride in these patients.
* Evaluate quality of life of these patients treated with pilocarpine hydrochloride.

Quality of life was assessed at baseline and then weekly for 6 weeks.

Pilocarpine in Treating Vaginal Dryness in Patients With Breast Cancer

Pilocarpine for Vaginal Dryness: A Phase III Randomized, Double Blind, Placebo-Controlled Study

Vaginal dryness was measured by the numerical analogue scale at baseline and through the six weeks of treatment. The item scores was transformed into 0 to 100 scales with 0=poor quality of life (QOL) and 100=best possible QOL. The average AUC values were calculated by dividing 6 from AUC values for participants who completed item on all 6 weeks. If a participant completed the item at baseline, week 1, 2 and 3 but did not complete the item at week 4 to week 6, the AUC values of the item was prorated, which is (((AUC values \* 6) / 3) / 6). The average pro-rated AUC for vaginal dryness scores was compared in each of the Pilocarpine arms against the collective placebo arm.

CTCAE Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death.

The impact of vaginal dryness for activities of daily living (ADL) were measured by the numerical analogue scales at baseline and through the six weeks of treatment. The item scores was transformed into 0 to 100 scales with 0=poor quality of life (QOL) and 100=best possible QOL. The average AUC values were calculated by dividing 6 from AUC values for participants who completed item on all 6 weeks. If a participant completed the item at baseline, week 1, 2 and 3 but did not complete the item at week 4 to week 6, the AUC values of the item was prorated, which is (((AUC values \* 6) / 3) / 6). The average pro-rated AUC scores was compared in each of the Pilocarpine arms against the collective placebo arm.

The impact of vaginal dryness for activities of daily living (ADL) were measured by the numerical analogue scales at baseline and through the six weeks of treatment. The item scores was transformed into 0 to 100 scales with 0=poor quality of life (QOL) and 100=best possible QOL. The change from baseline scores was calculated by subtracting the baseline item scores from the scores at 6 week.

Alliance for Clinical Trials in Oncology

Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.

Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.

Pilocarpine 2 Times Per Day

Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.

Pilocarpine 4 Times Per Day

Patients receive 1 capsule of placebo 2 times per day for 6 weeks and; patients receive 1 capsule of placebo 4 times per day for 6 weeks.

Collective Placebo

Total

Age, Continuous

Female

Sex/Gender, Customized

Race (NIH/OMB)

United States

Region of Enrollment

Unknown

Tamoxifen use

Current aromatase inhibitor

Mild

Moderate

Severe

Severity of vaginal symptoms

Breast cancer history

Dr. Charles L. Loprinzi

Includes all participants that reported a baseline value and at least one value after baseline (i.e. week 3, 4, 5 or 6).

Average Vaginal Dryness Scores Via Area Under the Curve (AUC) Summary Statistics

Comparison of Urinary Frequency among arms

Grade 1 or 2 rigors

Grade 1 or 2 urinary frequency

Grade 1 or 2 nausea

Grade 1 or 2 sweating

Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) 3.0

Interfered with general activity

Interfered with mood

Interfered with normal work

Interfered with relations with other people

Interfered with sleep

Interfered with enjoyment of life

Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living

Includes all participants who completed both baseline and week 6 assessments.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pilocarpine in Preventing Mucositis and Dry Mouth in Patients Receiving Radiation Therapy for Head and Neck Cancer	NCT00003139	Head and Neck C... Oral Complicati...	pilocarpine hyd... Placebo	18 Years - 120 Years	Radiation Therapy Oncology Group
Pilocarpine in Treating Vaginal Dryness in Patients With Breast Cancer	NCT00343382	Breast Cancer Vaginal Dryness	pilocarpine hyd... placebo	18 Years -	Alliance for Clinical Trials in Oncology
Pilocarpine in Preventing Mucositis and Dry Mouth in Patients Receiving Radiation Therapy for Head and Neck Cancer	NCT00003139	Head and Neck C... Oral Complicati...	pilocarpine hyd... Placebo	18 Years - 120 Years	Radiation Therapy Oncology Group

Spots Global Cancer Trial Database for pilocarpine hydrochloride