Pilocarpine in Treating Vaginal Dryness in Patients With Breast Cancer

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00343382
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 201
• Locations: 192
• Arms: 4
• Duration (Months): 72
• Patients Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Vaginal Dryness	Drug: pilocarpine hydrochloride; Other: placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 201 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Pilocarpine for Vaginal Dryness: A Phase III Randomized, Double Blind, Placebo-Controlled Study
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. Average Vaginal Dryness Scores Via Area Under the Curve (AUC) Summary Statistics [Baseline to Week 6]

   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

1. Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) 3.0 [End of 6 weeks]

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

2. Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living [Baseline to Week 6]

   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.

3. Change From Baseline to Week 6 on the Impact of Vaginal Dryness for Activities of Daily Living Scores [Baseline and Week 6]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
2	Boulder Community Hospital	Boulder	Colorado	United States	80301-9019
3	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
4	St. Anthony Central Hospital	Denver	Colorado	United States	80204
5	Porter Adventist Hospital	Denver	Colorado	United States	80210
6	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
7	St. Joseph Hospital	Denver	Colorado	United States	80218
8	Rose Medical Center	Denver	Colorado	United States	80220
9	CCOP - Colorado Cancer Research Program	Denver	Colorado	United States	80224-2522
10	Swedish Medical Center	Englewood	Colorado	United States	80110
11	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado	United States	81502
12	North Colorado Medical Center	Greeley	Colorado	United States	80631
13	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
14	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80501
15	McKee Medical Center	Loveland	Colorado	United States	80539
16	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado	United States	81004
17	North Suburban Medical Center	Thornton	Colorado	United States	80229
18	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
19	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
20	Graham Hospital	Canton	Illinois	United States	61520
21	Memorial Hospital	Carthage	Illinois	United States	62321
22	Eureka Community Hospital	Eureka	Illinois	United States	61530
23	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
24	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
25	Mason District Hospital	Havana	Illinois	United States	62644
26	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
27	McDonough District Hospital	Macomb	Illinois	United States	61455
28	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois	United States	61265
29		Moline	Illinois	United States	61265
30	OSF Holy Family Medical Center	Monmouth	Illinois	United States	61462
31	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
32	Community Cancer Center	Normal	Illinois	United States	61761
33	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
34	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
35	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
36	Proctor Hospital	Peoria	Illinois	United States	61614
37	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
38	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
39	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
40	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
41	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
42	Perry Memorial Hospital	Princeton	Illinois	United States	61356
43	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
44	Elkhart General Hospital	Elkhart	Indiana	United States	46515
45	Howard Community Hospital	Kokomo	Indiana	United States	46904
46	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
47	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
48	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
49	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
50	South Bend Clinic	South Bend	Indiana	United States	46617
51	McFarland Clinic, PC	Ames	Iowa	United States	50010
52		Bettendorf	Iowa	United States	52722
53	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
54	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
55	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
56	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
57	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
58	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
59	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
60	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
61	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
62	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
63	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
64	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
65	Southwest Medical Center	Liberal	Kansas	United States	67901
66	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
67	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
68	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
69	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
70	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
71	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
72	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
73	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
74	CCOP - Wichita	Wichita	Kansas	United States	67214
75	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
76	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
77	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
78	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
79	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
80	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
81	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
82	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
83	Hurley Medical Center	Flint	Michigan	United States	48503
84	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
85	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
86	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
87	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
88	Foote Memorial Hospital	Jackson	Michigan	United States	49201
89	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
90	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
91	Mercy General Health Partners	Muskegon	Michigan	United States	49443
92	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
93	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
94	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
95	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
96	Munson Medical Center	Traverse City	Michigan	United States	49684
97	St. John Macomb Hospital	Warren	Michigan	United States	48093
98	Metro Health Hospital	Wyoming	Michigan	United States	49519
99		Alexandria	Minnesota	United States	56308
100	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
101	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
102	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
103	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
104	CCOP - Duluth	Duluth	Minnesota	United States	55805
105	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
106	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
107		Fergus Falls	Minnesota	United States	56537
108	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
109	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
110	Meeker County Memorial Hospital	Lichfield	Minnesota	United States	55355
111	Immanuel St. Joseph's	Mankato	Minnesota	United States	56002
112	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
113	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
114	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
115	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
116	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
117	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
118	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
119	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
120	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
121	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
122	United Hospital	Saint Paul	Minnesota	United States	55102
123	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
124	Regions Hospital Cancer Care Center	St. Paul	Minnesota	United States	55101
125	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
126	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
127	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
128	St. John's Regional Health Center	Springfield	Missouri	United States	65804
129	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
130	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
131	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
132	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
133	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
134	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
135	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
136	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
137	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
138	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
139		Great Falls	Montana	United States	59405
140	Northern Montana Hospital	Havre	Montana	United States	59501
141	St. Peter's Hospital	Helena	Montana	United States	59601
142	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
143	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
144	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
145	Community Medical Center	Missoula	Montana	United States	59801
146	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
147	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
148	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
149	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
150	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
151	Immanuel Medical Center	Omaha	Nebraska	United States	68122
152	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
153	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
154	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
155	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
156	MeritCare Broadway	Fargo	North Dakota	United States	58122
157	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
158	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
159	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
160	CCOP - Columbus	Columbus	Ohio	United States	43215
161	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
162	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
163	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
164	Grady Memorial Hospital	Delaware	Ohio	United States	43015
165	Fairfield Medical Center	Lancaster	Ohio	United States	43130
166	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
167	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
168	Mercy Medical Center	Springfield	Ohio	United States	45504
169	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
170	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
171	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
172	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
173	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
174	Adventist Medical Center	Portland	Oregon	United States	97216
175	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
176	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
177	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
178	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
179	AnMed Cancer Center	Anderson	South Carolina	United States	29621
180	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
181	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
182	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
183	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
184	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
185	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037
186	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
187	Central Wisconsin Cancer Program at Agnesian HealthCare	Fond du Lac	Wisconsin	United States	54935
188	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
189	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
190	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
191	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
192	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Charles L. Loprinzi, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00343382
• Other Study ID Numbers: NCCTG-N04CA; NCI-2009-00648; CDR0000482969
• First Posted: Jun 23, 2006
• Last Update Posted: Aug 12, 2016
• Last Verified: Jul 1, 2016

• 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; Pilocarpine

Study Results

Participant Flow

Recruitment Details	Two-hundred and one (201) participants were recruited between December 2006 and May 2009 from 22 North Central Cancer Treatment Group (NCCTG) member sites.
Pre-assignment Detail	Five participants (2 collective placebo, 2 Pilocarpine 2 times per day, 1 Pilocarpine 4 times per day) canceled prior to study medication begins and one Pilocarpine 2 times per day participant was ineligible. These six participants were excluded from all analysis.

Arm/Group Title	Collective Placebo	Pilocarpine 2 Times Per Day	Pilocarpine 4 Times Per Day
Arm/Group Description	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.	Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.
Period Title: Overall Study
STARTED	64	65	66
COMPLETED	60	51	49
NOT COMPLETED	4	14	17

Baseline Characteristics

Arm/Group Title	Collective Placebo	Pilocarpine 2 Times Per Day	Pilocarpine 4 Times Per Day	Total
Arm/Group Description	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.	Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.	Total of all reporting groups
Overall Participants	64	65	66	195
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.6 (7.93)	55.1 (8.14)	54.7 (7.25)	54.8 (7.74)
Sex/Gender, Customized (participants) [Number]
Female	64 100%	65 100%	66 100%	195 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.6%	0 0%	1 1.5%	2 1%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	3 4.7%	1 1.5%	0 0%	4 2.1%
White	60 93.8%	63 96.9%	65 98.5%	188 96.4%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 1.5%	0 0%	1 0.5%
Region of Enrollment (participants) [Number]
United States	64 100%	65 100%	66 100%	195 100%
Tamoxifen use (participants) [Number]
Yes	10 15.6%	10 15.4%	9 13.6%	29 14.9%
No	54 84.4%	54 83.1%	56 84.8%	164 84.1%
Unknown	0 0%	1 1.5%	1 1.5%	2 1%
Current aromatase inhibitor (participants) [Number]
Yes	36 56.3%	37 56.9%	38 57.6%	111 56.9%
No	28 43.8%	27 41.5%	27 40.9%	82 42.1%
Unknown	0 0%	1 1.5%	1 1.5%	2 1%
Severity of vaginal symptoms (participants) [Number]
Mild	6 9.4%	6 9.2%	6 9.1%	18 9.2%
Moderate	30 46.9%	30 46.2%	30 45.5%	90 46.2%
Severe	28 43.8%	29 44.6%	30 45.5%	87 44.6%
Breast cancer history (participants) [Number]
Yes	55 85.9%	59 90.8%	58 87.9%	172 88.2%
No	9 14.1%	6 9.2%	8 12.1%	23 11.8%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Collective Placebo	Pilocarpine 2 Times Per Day	Pilocarpine 4 Times Per Day
Arm/Group Description	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.	Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.
Measure Participants	61	61	55
Mean (Standard Deviation) [units on a scale]	63.6 (24.04)	55.8 (27.69)	66.0 (21.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Collective Placebo, Pilocarpine 2 Times Per Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1675
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Collective Placebo, Pilocarpine 4 Times Per Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5974
	Comments
	Method	Kruskal-Wallis
	Comments

2. Secondary Outcome

Title	Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) 3.0
Description	CTCAE Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death.
Time Frame	End of 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Collective Placebo	Pilocarpine 2 Times Per Day	Pilocarpine 4 Times Per Day
Arm/Group Description	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.	Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.
Measure Participants	63	65	66
Grade 1 or 2 rigors	2 3.1%	14 21.5%	17 25.8%
Grade 1 or 2 urinary frequency	12 18.8%	21 32.3%	29 43.9%
Grade 1 or 2 nausea	7 10.9%	16 24.6%	20 30.3%
Grade 1 or 2 sweating	19 29.7%	29 44.6%	33 50%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Collective Placebo, Pilocarpine 2 Times Per Day, Pilocarpine 4 Times Per Day
	Comments	Comparison of Rigors among arms.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Collective Placebo, Pilocarpine 2 Times Per Day, Pilocarpine 4 Times Per Day
	Comments	Comparison of Urinary Frequency among arms
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Collective Placebo, Pilocarpine 2 Times Per Day, Pilocarpine 4 Times Per Day
	Comments	Comparison of nausea among arms
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Collective Placebo, Pilocarpine 2 Times Per Day, Pilocarpine 4 Times Per Day
	Comments	Comparison of sweating among arms
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.062
	Comments
	Method	Kruskal-Wallis
	Comments

3. Secondary Outcome

Title	Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living
Description	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.
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Collective Placebo	Pilocarpine 2 Times Per Day	Pilocarpine 4 Times Per Day
Arm/Group Description	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.	Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.
Measure Participants	62	61	55
Interfered with general activity	87.9 (15.77)	87.1 (15.36)	87.0 (15.72)
Interfered with mood	85.4 (17.17)	75.8 (24.16)	81.8 (17.65)
Interfered with normal work	91.5 (14.08)	93.0 (11.77)	92.3 (10.80)
Interfered with relations with other people	82.2 (20.62)	77.9 (25.92)	80.6 (21.27)
Interfered with sleep	93.0 (13.46)	92.3 (15.81)	93.3 (9.28)
Interfered with enjoyment of life	77.8 (24.24)	68.7 (27.84)	76.4 (23.08)

4. Secondary Outcome

Title	Change From Baseline to Week 6 on the Impact of Vaginal Dryness for Activities of Daily Living Scores
Description	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.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Collective Placebo	Pilocarpine 2 Times Per Day	Pilocarpine 4 Times Per Day
Arm/Group Description	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.	Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.
Measure Participants	58	58	54
Interfered with general activity	17.8 (26.23)	16.0 (28.77)	16.1 (27.02)
Interfered with mood	18.3 (29.03)	17.8 (29.44)	18.9 (34.62)
Interfered with normal work	11.0 (23.15)	6.0 (18.16)	9.1 (22.17)
Interfered with relations with other people	23.0 (37.41)	18.5 (33.02)	24.3 (41.15)
Interfered with sleep	5.6 (19.27)	5.1 (12.75)	10.8 (21.99)
Interfered with enjoyment of life	26.7 (35.17)	21.1 (36.11)	30.2 (33.14)

Adverse Events

Time Frame	End of 6 Weeks
Adverse Event Reporting Description	Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Arm/Group Title	Pilocarpine 2 Times Per Day		Pilocarpine 4 Times Per Day		Collective Placebo
Arm/Group Description	Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.		Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.		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.
All Cause Mortality
	Pilocarpine 2 Times Per Day		Pilocarpine 4 Times Per Day		Collective Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Pilocarpine 2 Times Per Day		Pilocarpine 4 Times Per Day		Collective Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		0/66 (0%)		0/63 (0%)
Other (Not Including Serious) Adverse Events
	Pilocarpine 2 Times Per Day		Pilocarpine 4 Times Per Day		Collective Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/65 (73.8%)		47/66 (71.2%)		33/63 (52.4%)
Eye disorders
Flashing vision	1/65 (1.5%)	1	0/66 (0%)	0	0/63 (0%)	0
Gastrointestinal disorders
Abdominal distension	1/65 (1.5%)	1	0/66 (0%)	0	0/63 (0%)	0
Diarrhea	0/65 (0%)	0	1/66 (1.5%)	1	0/63 (0%)	0
Dry mouth	0/65 (0%)	0	0/66 (0%)	0	1/63 (1.6%)	1
Flatulence	1/65 (1.5%)	1	0/66 (0%)	0	0/63 (0%)	0
Gastrointestinal disorder	0/65 (0%)	0	3/66 (4.5%)	3	1/63 (1.6%)	1
Nausea	16/65 (24.6%)	16	20/66 (30.3%)	20	7/63 (11.1%)	7
Salivary gland disorder	0/65 (0%)	0	2/66 (3%)	2	0/63 (0%)	0
General disorders
Rigors	14/65 (21.5%)	14	17/66 (25.8%)	17	2/63 (3.2%)	2
General symptom	1/65 (1.5%)	1	0/66 (0%)	0	0/63 (0%)	0
Nervous system disorders
Dizziness	10/65 (15.4%)	10	13/66 (19.7%)	13	6/63 (9.5%)	6
Headache	1/65 (1.5%)	1	0/66 (0%)	0	0/63 (0%)	0
Renal and urinary disorders
Urinary frequency	21/65 (32.3%)	21	29/66 (43.9%)	29	12/63 (19%)	12
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	21/65 (32.3%)	21	25/66 (37.9%)	25	14/63 (22.2%)	14
Skin and subcutaneous tissue disorders
Pruritus	1/65 (1.5%)	1	0/66 (0%)	0	0/63 (0%)	0
Rash desquamating	1/65 (1.5%)	1	0/66 (0%)	0	0/63 (0%)	0
Sweating	29/65 (44.6%)	29	33/66 (50%)	33	19/63 (30.2%)	19
Urticaria	1/65 (1.5%)	1	0/66 (0%)	0	0/63 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.