Solifenacin Compared to Clonidine for Reducing Hot Flashes Among Breast Cancer Patients

Study Overview
=================
Brief Summary
-----------------
Hot flashes present a considerable problem for many breast cancer patients; these symptoms may be intensified by hormonal therapies, such as aromatase inhibitors or tamoxifen. This study examines the value of solifenacin (a muscarinic acetylcholine receptor antagonist) in reducing hot flashes, compared with clonidine (a medication often used for treating hot flashes).

Detailed Description
-----------------
There has been considerable interest in developing new treatment strategies for managing hot flashes among women with breast cancer, in view of the limitations associated with currently available treatments. This randomized study evaluates the safety and efficacy of 3 weeks of solifenacin compared to 3 weeks of clonidine, for women receiving adjuvant hormonal therapy (aromatase inhibitors or tamoxifen) for breast cancer.

Official Title
-----------------
A Phase II Randomized Study of Solifenacin Compared to Clonidine for Reducing Hot Flashes Among Breast Cancer Patients Receiving Adjuvant Hormonal Therapy

Conditions
-----------------
Hot Flashes, Breast Cancer

Intervention / Treatment
-----------------
* Drug: solifenacin
* Drug: Clonidine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women with a history of invasive breast cancer or DCIS Currently taking aromatase inhibitors or tamoxifen Not receiving hormone replacement therapy for minimum of one month Age 18 years or older Self-reported hot flashes at least fourteen times per week Self-reported hot flashes for at least one month If receiving non-tricyclic antidepressants (venlafaxine, paroxetine, citalopram, sertraline, etc.) or gabapentin, no change in regimen in past 4 weeks. Exclusion Criteria: Receiving any other treatment for hot flashes within the past month, including estrogens, progestins, androgens, or gabapentin. Current use of clonidine or solifenacin. (If patients have been off of these for one month, then they are eligible) History of severe renal or moderate or severe hepatic impairment, as indicated by physical exam and medical record Concurrent or planned chemotherapy or radiotherapy (within next 3 months) Currently receiving tricyclic antidepressants, monoamine oxidase inhibitors, barbiturates, pimozide. Currently using CYP3A4 inducers (i.e., aminoglutethimide, carbamazepine, dexamethasone, efavirenz, ethosuximide, griseofulvin, modafinil, nafcillin, nevirapine, oxcarbazepine, phenobarbital, phenylbutazone, phenytoin, primidone, rifabutin, rifampin, rifapentine, St. John's Wort, sulfadimidine, sulfinpyrazone, troglitazone) or potent CYP3A4 inhibitors (i.e., chloramphenicol, clarithromycin, erythromycin, imatinib mesylate, indinavir sulfate, itraconazole, ketoconazole, nefazoldone, nelfinavir mesylate, ritonavir, telithromycin, troleandomycin). Uncontrolled or poorly controlled narrow-angle glaucoma, urinary retention, gastric retention (evaluated from history & physical exam and medical record) Hypotension or uncontrolled hypertension (160/95 > BP < 100/60) Severe coronary insufficiency, conduction disturbances, recent myocardial infarction (within past 3 months), cerebrovascular disease, syncope (evaluated from history & physical and medical record) History of allergy or adverse reactions to clonidine or solifenacin ECOG status > 2 (in bed more than 50% of day)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: solifenacin<br>oral solifenacin 5.0 mg daily for 3 weeks | Drug: solifenacin<br>* oral solifenacin 5.0 mg daily for 3 weeks<br>* Other names: Vesicare;|
| Active Comparator: clonidine<br>oral clonidine 0.1 mg daily for 3 weeks | Drug: Clonidine<br>* oral clonidine 0.1 mg daily for 3 weeks<br>* Other names: Catapres, Dixarit;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: hot flash composite and frequency scores (daily diary) | to evaluate changes in hot flash composite and frequency scores for women receiving 3 weeks of oral solifenacin compared to those receiving 3 weeks of oral clonidine | from baseline to end of treatment (3 weeks) | 
| Safety: number of clinician-rated adverse events | to evaluate changes in number of adverse events for women receiving 3 weeks of oral solifenacin compared to those receiving 3 weeks of oral clonidine | from consent until end of study (approximately 9 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| daily functioning (Hot Flash-Related Daily Interference score) | to evaluate changes in daily functioning (Hot Flash-Related Daily Interference Score) for women receiving 3 weeks of oral solifenacin compared to those receiving 3 weeks of oral clonidine | from baseline to end of treatment (3 weeks) | 
| sleep (Insomnia Severity Index) | To evaluate changes in sleep | from baseline to end of treatment (3 weeks) | 
| quality of life (Illness Cognition Questionnaire, SF-12) | to evaluate changes in health-related quality of life. (Additional analyses will be observational, exploring associations between quality of life and meaning-making.) | from baseline to end of treatment (3 weeks) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hot flashes, breast cancer, aromatase inhibitors, solifenacin, clonidine, quality of life