Pregabalin in Treating Women With Hot Flashes

Study Overview
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Brief Summary
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RATIONALE: Pregabalin may help relieve hot flashes in women with a history of breast cancer or those who have no history and do not wish to take estrogen therapy for fear of increased risk of breast cancer. It is not yet known what dose of pregabalin may be more effective in treating hot flashes. PURPOSE: This is a randomized phase III trial to determine the efficacy of two doses of pregabalin, in comparison to placebo, in the prevention of hot flashes.

Detailed Description
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OBJECTIVES: To evaluate the efficacy of 150 mg of pregabalin versus placebo on hot flash scores in women with a history of breast cancer or women who do not wish to take estrogen therapy for fear of increased risk of breast cancer. To evaluate the side effect profile of different doses of pregabalin in these patients. To evaluate the effect of 150 mg of pregabalin versus placebo on the secondary outcome of interference of activities from hot flashes in these patients. To evaluate the efficacy and side effect profile of 75 mg of pregabalin versus placebo in these patients. OUTLINE: Patients are stratified according to age (18-49 years vs ≥ 50 years); selective estrogen-receptor modulator (i.e., tamoxifen or raloxifene) or aromatase inhibitor use (yes vs no); duration of hot flashes (< 9 months vs ≥ 9 months); and frequency of hot flashes per 24-hour period (4-9 vs ≥ 10). Patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive 75 mg of oral pregabalin twice daily for 6 weeks. Arm II: Patients receive 150 mg of oral pregabalin twice daily for 6 weeks. Arm III: Patients receive oral placebo twice daily for 6 weeks. Treatment in all arms continues in the absence of unacceptable toxicity. Patients complete Hot Flash Diaries at baseline and once daily during treatment and the Symptom Experience Diary at baseline and once weekly during treatment. Patients also complete the Profile of Mood States and the Hot Flash Related Daily Interference Scale questionnaires at baseline and after completion of study treatment.

Official Title
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A Phase III, Randomized, Double-Blind, Placebo-Controlled Evaluation of Pregabalin for Alleviating Hot Flashes

Conditions
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Breast Cancer, Hot Flashes

Intervention / Treatment
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* Drug: pregabalin
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Meeting 1 of the following criteria: History of breast cancer (currently without malignant disease) No history of breast cancer, but patient wishes to avoid estrogen due to a perceived increased risk of breast cancer Bothersome hot flashes (defined by their occurrence ≥ 28 times per week and of sufficient severity to make the patient desire therapeutic intervention) Presence of hot flashes for ≥ 1 month prior to study entry PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Life expectancy ≥ 6 months Able to complete questionnaire(s) by themselves or with assistance Women of childbearing potential not eligible (per the judgment of the attending clinician) Serum creatinine ≤ 1.5 times upper limit of normal PRIOR CONCURRENT THERAPY: No prior gabapentin or pregabalin More than 4 weeks since prior and no concurrent antineoplastic chemotherapy, androgens, estrogens, or progestational agents Vaginal estrogen is allowed if used for the past month and not planned to be discontinued Concurrent adjuvant targeted therapy (i.e., lapatinib, trastuzumab [Herceptin®]) allowed in patients with no evidence of disease Concurrent tamoxifen, raloxifene, or aromatase inhibitors on a constant dose for at least 4 weeks allowed provided the medication will not be stopped during the study period No concurrent or planned use of other agents for hot flashes except for any of the following: Stable dose of vitamin E is allowed as long as agent was started > 30 days prior to study initiation and is to be continued throughout the study period Soy is allowed, if it is planned to be continued at the same dose during the study period Stable dose of antidepressants is allowed as long as it was started > 30 days prior to study initiation and is to be continued at a stable dose throughout the study period

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregabalin75<br>Patients receive 75 mg of oral pregabalin twice daily for 6 weeks. | Drug: pregabalin<br>* Given orally<br>|
| Experimental: Pregabalin150<br>Patients receive 150 mg of oral pregabalin twice daily for 6 weeks. | Drug: pregabalin<br>* Given orally<br>|
| Placebo Comparator: Placebo<br>Patients receive oral placebo twice daily for 6 weeks. | Other: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical Change From Baseline in Hot Flash Score at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases). | Hot flash activity will be analyzed in a number of ways. For the primary analysis, the numerical change-from-baseline to hot flash score after week 6 of treatment will be compared between the highest dose treatment arm and the placebo arm. A hot flash score is computed for each patient by assigning points (1=mild, 2=moderate, 3=severe, 4=very severe) to each hot flash based on patient-reported severity, adding the points for each day, and averaging across each week of the study. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA). | Baseline, after week 6 of treatment | 
| Percent Change From Baseline in Hot Flash Score at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases). | Hot flash activity will be analyzed in a number of ways. For the primary analysis, the percent change-from-baseline to hot flash score after week 6 of treatment will be compared between the highest dose treatment arm and the placebo arm. A hot flash score is computed for each patient by assigning points (1=mild, 2=moderate, 3=severe, 4=very severe) to each hot flash based on patient-reported severity, adding the points for each day, and averaging across each week of the study. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA). | Baseline, after week 6 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical Change From Baseline in Hot Flash Frequency at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases). | The analysis of daily average hot flash frequency will follow as specified for the primary analysis. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA). | Baseline, after week 6 of treatment | 
| Percent Change From Baseline in Hot Flash Frequency at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases). | The analysis of daily average hot flash frequency will follow as specified for the primary analysis. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA). | Baseline, after week 6 of treatment | 
| Comparison of 75 mg of Pregabalin vs Placebo, Numerical Change From Baseline in Hot Flash Score at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases). | Hot flash activity will be analyzed in a number of ways. For the this analysis, the numerical change-from-baseline to hot flash score after week 6 of treatment will be compared between the lower dose treatment arm and the placebo arm. A hot flash score is computed for each patient by assigning points (1=mild, 2=moderate, 3=severe, 4=very severe) to each hot flash based on patient-reported severity, adding the points for each day, and averaging across each week of the study. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA). | Baseline, after week 6 of treatment | 
| Comparison of 75 mg of Pregabalin vs Placebo. Percent Change From Baseline in Hot Flash Score at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases). | Hot flash activity will be analyzed in a number of ways. For the this analysis, the percent change-from-baseline to hot flash score after week 6 of treatment will be compared between the lower dose treatment arm and the placebo arm. A hot flash score is computed for each patient by assigning points (1=mild, 2=moderate, 3=severe, 4=very severe) to each hot flash based on patient-reported severity, adding the points for each day, and averaging across each week of the study. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA). | Baseline, after week 6 of treatment | 
| Toxicity Data for the Individual Study Arms From the Symptom Experience Diary . | A descriptive report of the toxicities experienced by participants will be measured with a Symptom Experience Diary. Participants will complete this questionnaire weekly. This patient diary contains several questions related to potential side effects and side benefits of pregabalin measured on a numeric analogue scale (based on 0-10 scale with 10 being worst toxicity, providing numbers representing the worst median changes from baseline minus Maximum (Week 1-6) Symptom Experience Diary Distributions). | Baseline, 6 weeks during treatment. | 
| Mood and Hot Flash-related Daily Interference on Activities After 6 Weeks of Treatment | Endpoints for this analysis will be median change from baseline to after week 6 of treatment. Hot Flash Related Daily Interference Scale is used to evaluate the specific impact of the study treatment on the effect hot flashes have on various life activities such as work, social, leisure and relationships. Responses to the questionnaire are recorded on a 0 to 10 scale. Lower scores are better. | Baseline, after week 6 of treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, hot flashes