Pilocarpine in Treating Vaginal Dryness in Patients With Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00343382
First received: June 22, 2006
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Vaginal Dryness
Drug: pilocarpine hydrochloride
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: Pilocarpine for Vaginal Dryness: A Phase III Randomized, Double Blind, Placebo-Controlled Study

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Average Vaginal Dryness Scores Via Area Under the Curve (AUC) Summary Statistics [ Time Frame: Baseline to Week 6 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) 3.0 [ Time Frame: End of 6 weeks ] [ Designated as safety issue: Yes ]
    CTCAE Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death.

  • Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living [ Time Frame: Baseline to Week 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 6 on the Impact of Vaginal Dryness for Activities of Daily Living Scores [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    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.


Enrollment: 201
Study Start Date: December 2006
Study Completion Date: December 2012
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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
Given orally
Experimental: Arm II
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
Given orally
Placebo Comparator: Arm III
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
Given orally
Placebo Comparator: Arm IV
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
Given orally

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00343382

  Show 192 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Charles L. Loprinzi, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Loprinzi CL, Balcueva EP, Liu H, et al.: A phase III randomized, double-blind, placebo-controlled study of pilocarpine for vaginal dryness: NCCTG study N04CA. [Abstract] J Clin Oncol 28 (Suppl15): A-9024, 2010.

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00343382     History of Changes
Other Study ID Numbers: NCCTG-N04CA, NCI-2009-00648, CDR0000482969
Study First Received: June 22, 2006
Results First Received: July 16, 2014
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Trials in Oncology:
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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Pilocarpine
Autonomic Agents
Cholinergic Agents
Cholinergic Agonists
Miotics
Molecular Mechanisms of Pharmacological Action
Muscarinic Agonists
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014