Pilocarpine in Treating Vaginal Dryness in Patients With Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer, Vaginal Dryness

Intervention / Treatment
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* Drug: pilocarpine hydrochloride
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Required Characteristics: Adult post menopausal women or women with no childbearing potential (≥ 18 years) with a history of breast cancer (currently no evidence of disease) or women who do not want to take vaginal estrogen for a fear of an increased risk of breast cancer. Postmenopausal status will be determined by the primary physician. Significant vaginal complaints defined as persistent vaginal dryness and/or itching of sufficient severity to make a patient desire therapeutic intervention. Symptoms should have been present ≥ 2 months prior to randomization. Life expectancy > 6 months Ability to complete questionnaire(s) by themselves or with assistance. Contraindications: Initiation or discontinuation of tamoxifen or aromatase inhibitors ≤2 months prior to randomization or plans to initiate or discontinue any of these medications during the 6-week study. Active vaginal infection Concurrent chemotherapy Acute iritis Current or past use of pilocarpine (regardless of purpose) Planned use of any vaginal preparations during the study period (including any over the counter or herbal preparations). Note: Lubricants used during sexual intercourse are permitted. Use of any vaginal preparations ≤ 1 week prior to study entry (Exception: If patient has used vaginal preparations during the previous week but will stop, then they can be placed on study with plans to start with pretreatment questionnaire one week later). Note: Lubricants used during sexual intercourse are permitted. Current (≤ 4weeks prior to randomization), or planned during the study period, use of any estrogen product. A diagnosis of asthma, COPD, CAD or narrow angle glaucoma, or known cholelithiasis. Hepatic or renal insufficiency defined as a history of an elevation of SGOT ≥1.5 x ULN or creatinine ≥ 1.5 x ULN within the past year. Concurrent use of other anticholinergics Use of pharmacologic soy preparations Known history of cardiac arrhythmia. (Patients with occasional PVC's or PAC's that do not require treatment are eligible.) Prior or concurrent pelvic radiation therapy Prior radical pelvic surgery (TAH/BSO is allowed) Use of beta adrenergic antagonists Diagnosis of any of the following conditions: Vulvar and vaginal dysplasia Essential vulvodynia Vulvar vestibulitis Vaginal prolapse Bartholin cyst/abscess History of Bartholin gland surgery Lichen sclerosis Lichen planus of the vulvovaginal region Desquamative vaginitis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Drug: pilocarpine hydrochloride<br>* Given orally<br>|
| Experimental: Arm II<br>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. | Drug: pilocarpine hydrochloride<br>* Given orally<br>|
| Placebo Comparator: Arm III<br>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. | Other: placebo<br>* Given orally<br>|
| Placebo Comparator: Arm IV<br>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. | Other: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Vaginal Dryness Scores Via Area Under the Curve (AUC) Summary Statistics | 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. | Baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) 3.0 | CTCAE Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death. | End of 6 weeks | 
| Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living | 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. | Baseline to Week 6 | 
| Change From Baseline to Week 6 on the Impact of Vaginal Dryness for Activities of Daily Living Scores | 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. | Baseline and Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sexuality and reproductive issues, sexual dysfunction, recurrent breast cancer, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer