Pilocarpine in Treating Vaginal Dryness in Patients With Breast Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00343382
• Other study ID #: NCCTG-N04CA
• Secondary ID: NCI-2009-00648CD
• Status: Completed
• Phase: Phase 3
• First received: June 22, 2006
• Last updated: September 24, 2014
• Start date: December 2006
• Est. completion date: December 2012

Study information

• Verified date: September 2014
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 201
• Est. completion date: December 2012
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Vaginal Dryness

Intervention

Drug:
• pilocarpine hydrochloride
Given orally

Other:
• placebo
Given orally

Locations

Country	Name	City	State
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	McFarland Clinic, PC	Ames	Iowa
United States	AnMed Cancer Center	Anderson	South Carolina
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Boulder Community Hospital	Boulder	Colorado
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Grady Memorial Hospital	Delaware	Ohio
United States	CCOP - Colorado Cancer Research Program	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Anthony Central Hospital	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Swedish Medical Center	Englewood	Colorado
United States	Eureka Community Hospital	Eureka	Illinois
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Central Wisconsin Cancer Program at Agnesian HealthCare	Fond du Lac	Wisconsin
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Howard Community Hospital	Kokomo	Indiana
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Southwest Medical Center	Liberal	Kansas
United States	Meeker County Memorial Hospital	Lichfield	Minnesota
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	McDonough District Hospital	Macomb	Illinois
United States	Immanuel St. Joseph's	Mankato	Minnesota
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	OSF Holy Family Medical Center	Monmouth	Illinois
United States	Mercy General Health Partners	Muskegon	Michigan
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Adventist Medical Center	Portland	Oregon
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Perry Memorial Hospital	Princeton	Illinois
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	Mercy Medical Center	Springfield	Ohio
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan
United States	Regions Hospital Cancer Care Center	St. Paul	Minnesota
United States	North Suburban Medical Center	Thornton	Colorado
United States	Munson Medical Center	Traverse City	Michigan
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. John Macomb Hospital	Warren	Michigan
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	Metro Health Hospital	Wyoming	Michigan
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Loprinzi CL, Balcueva EP, Liu H, Sloan JA, Kottschade LA, Stella PJ, Carlson MD, Moore DF Jr, Zon RT, Levitt R, Jaslowski AJ. A phase III randomized, double-blind, placebo-controlled study of pilocarpine for vaginal dryness: North Central Cancer Treatment — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No