REDucing Hot FLASHes in Women Using Endocrine Therapy.

Study Overview
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Brief Summary
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The goal of this randomized intrapatient cross-over study is to assess the efficacy of oxybutynin versus venlafaxine in reducing hot flashes in women using endocrine therapy after breast cancer. The objectives it aims to answer are: To assess the efficacy of oxybutynin versus venlafaxine in reducing hot flashes in women using endocrine therapy after breast cancer To assess side effects of oxybutynin versus venlafaxine. To assess the personal preference of women for oxybutynin versus venlafaxine in reducing hot flashes. To assess quality of life of women when reducing hot flashes in women using endocrine therapy after breast cancer. Participants will fill-out a patient diary during 15 weeks total on a daily basis and receive an (online) questionnaire three times total. Researchers will compare two groups (venlafaxine group versus oxubutynine group) to assess its efficacy concerning hot flashes.

Official Title
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A Randomized Intrapatient Cross-over Study to Assess the Efficacy of Oxybutynin Versus Venlafaxine in Reducing Hot Flashes in Women Using Endocrine Therapy After Breast Cancer.

Conditions
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Breast Cancer, Hot Flash Due to Medication

Intervention / Treatment
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* Drug: Oxybutynin
* Drug: Venlafaxine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-, peri- or postmenopausal women of 18 years or above; Indication for endocrine therapy and already started with tamoxifen, aromatase inhibitors or luteinizing hormone-releasing hormone analogues for at least 4 weeks and planning to continue for the duration of the study; Experiencing hot flashes with a minimum of 14 per week for at least 1 month and desire to start a pharmacologic intervention. Exclusion Criteria: Pregnant; Breast feeding; Patients who receive chemotherapy or immunotherapy/HER2 antibodies within the prior 8 weeks, and patients scheduled for chemotherapy during the study period; Palliative setting; Use of venlafaxine or any other antidepressants, also including St. John's wort within the previous year; Creatinine clearance < 30 ml/min; Liver cirrhosis; Use of gabapentin and/or calcium channel antagonists within 2 weeks of study entry; Use of oxybutynin before study entry; Use of any other substances or therapies for the treatment of hot flashes, for instance acupuncture.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Venlafaxine<br>In this open-label randomized controlled intrapatient cross-over study patients are randomly assigned to one of the two treatment groups. After a one week baseline period, group 1 starts with venlafaxine 37.5 mg once daily for 7 days followed by 75 mg once daily for 5 weeks followed by a two-week wash-out period (no medication), hereafter the group starts with oxybutynin 5 mg twice per day for 6 weeks total. | Drug: Oxybutynin<br>* Oxybutynin 5 mg twice per day for 6 weeks<br>Drug: Venlafaxine<br>* Venlafaxine 37.5 mg once daily for 7 days followed by 75 mg once daily for 5 weeks<br>|
| Experimental: Oxybutynin<br>After a one week baseline period, group 2 starts with oxybutynin 5 mg twice per day for 6 weeks total followed by a two-week wash-out period (no medication), hereafter the group starts with venlafaxine 37.5 mg once daily for 7 days followed by 75mg once daily for 5 weeks. | Drug: Oxybutynin<br>* Oxybutynin 5 mg twice per day for 6 weeks<br>Drug: Venlafaxine<br>* Venlafaxine 37.5 mg once daily for 7 days followed by 75 mg once daily for 5 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and severity of hot flashes | Number and severity of hot flashes during 6-weeks of therapy measured by the Hot Flash Diary. | 15 weeks total | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life and health status | Quality of life and health status at baseline and after 6 weeks of treatment measured by the EORTC-QLQ-C30 | 15 weeks total | 
| Adverse effects of treatments | Adverse effects of treatments weekly measured by the National Cancer Institute Common Toxicity Criteria scale, version 5 | 15 weeks total | 
| Sleep quality | Sleep quality at baseline and after 6 weeks of treatment measured by the Groningen Sleep Quality Scale (GSQ) | 15 weeks total | 
| Anxiety and depression | Anxiety and depression measured at baseline and after 6 weeks of treatment with the Hospital Anxiety and Depression Scale (HADS) | 15 weeks total | 
| Sexual function | Sexual function measured at baseline and after 6 weeks of treatment with the Sexual Activity Questionnaire (SAQ) | 15 weeks total | 
| Cognitive function | Cognitive function measured at baseline and after 6 weeks of treatment with the 6-item cognitive impairment test (6-CIT) | 15 weeks total | 
| Adherence | Ask patients the following question after 6 weeks of treatment: 'Would you like to continue the endocrine therapy for the recommended duration of therapy taking the current medication (oxybutynin or venlafaxine) given the number and severity of hot flashes you experience during the last week?' | 15 weeks total | 
| Preference | Ask patients the following question after 6 weeks of the final treatment: 'Do you have a preference taking the medication from study period 1 or study period 2?' | 15 weeks total |