Pilocarpine in Treating Vaginal Dryness in Patients With Breast Cancer

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Breast Cancer; Vaginal Dryness

Treatments: Drug: pilocarpine hydrochloride; Other: placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00343382

NCI-2009-00648 (Registry Identifier)

NCCTG-N04CA

CDR0000482969 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 201 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Required Characteristics:

1. 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.
2. 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.
3. Life expectancy > 6 months
4. Ability to complete questionnaire(s) by themselves or with assistance.

Contraindications:

1. 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.

2. Active vaginal infection

3. Concurrent chemotherapy

4. Acute iritis

5. Current or past use of pilocarpine (regardless of purpose)

6. 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.

7. 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.

8. Current (≤ 4weeks prior to randomization), or planned during the study period, use of any estrogen product.

9. A diagnosis of asthma, COPD, CAD or narrow angle glaucoma, or known cholelithiasis.

10. 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.

11. Concurrent use of other anticholinergics

12. Use of pharmacologic soy preparations

13. Known history of cardiac arrhythmia. (Patients with occasional PVC's or PAC's that do not require treatment are eligible.)

14. Prior or concurrent pelvic radiation therapy

15. Prior radical pelvic surgery (TAH/BSO is allowed)

16. Use of beta adrenergic antagonists

17. 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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201 participants in 4 patient groups, including a placebo group

Arm I

Experimental group

Description:

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.

Treatment:

Drug: pilocarpine hydrochloride

Arm II

Experimental group

Description:

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.

Treatment:

Drug: pilocarpine hydrochloride

Arm III

Placebo Comparator group

Description:

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.

Treatment:

Other: placebo

Arm IV

Placebo Comparator group

Description:

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.

Treatment:

Other: placebo