Magnesium Oxide in Treating Postmenopausal Women With Hot Flashes and a History of Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Magnesium oxide may help relieve hot flashes symptoms in women with a history of breast cancer. PURPOSE: This randomized clinical trial studies how well a high-dose or a low-dose of magnesium oxide works compared to placebo in treating menopausal women with hot flashes and a history of breast cancer.

Detailed Description
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OBJECTIVES: Primary Evaluate the efficacy of magnesium oxide on hot flashes in women with a history of breast cancer. Secondary Evaluate the side-effect profile of magnesium oxide in this study population. Evaluate the effect of magnesium oxide on the secondary outcomes hot flash frequencies, hot flash severities, toxicities (including diarrhea), and hot flash-related daily interference on activities. Evaluate the effect of magnesium oxide on the change of magnesium level (for the first 150 patients). OUTLINE: This is a multicenter study. Patients are stratified according to age (18-49 years vs ≥ 50 years), current tamoxifen and/or selective estrogen receptor modulator (yes vs no), current aromatase inhibitor (yes vs no), and daily frequency of hot flashes (4-9 vs ≥ 10). Patients are randomized to 1 of 4 treatment arms. Arm I: Patients receive a low-dose of magnesium oxide orally (PO) daily (QD). Arm II: Patients receive a high-dose of magnesium oxide PO QD. Arm III: Patients receive a low-dose of placebo PO QD. Arm IV: Patients receive a high-dose of placebo PO QD. In all arms, treatment continues for 8 weeks in the absence of unacceptable toxicity. Some patients may continue or crossover to receive magnesium for 4 more weeks. Patients complete the Hot Flash Diary daily for 9 weeks beginning 1 week before treatment. They also complete the Symptom Experience Questionnaire, the Profile of Mood States (POMS), and Hot Flash-Related Daily Interference Scale (HFRDIS) questionnaires periodically during study treatment. Patients undergo blood sample collection at baseline and at the end of weeks 5 and 9 for serum magnesium level analysis.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study of Magnesium Supplements to Reduce Menopausal Hot Flashes

Conditions
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Breast Cancer, Cancer Survivor, Hot Flashes

Intervention / Treatment
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* Drug: magnesium oxide
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Women with a history of breast cancer (currently without malignant disease) 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 ≥ 30 days prior to study registration Willingness to provide the biologic specimens as required by the protocol Hormone receptor status not specified PATIENT CHARACTERISTICS: Women who are postmenopausal as defined by absence of a period in the past 12 months or bilateral oophorectomy Women with at least one ovary but without a uterus should be deemed postmenopausal by either age over 55 or a combination of estrogen within a postmenopausal range (per local lab) and FSH over 40 mIU/mL No women of childbearing potential or who are premenopausal Creatinine clearance > 30 mL/min Ability to complete questionnaire(s) by themselves or with assistance ECOG performance status 0 or 1 No history of allergic or other adverse reaction to magnesium No diabetes No patients with conditions that are implicated in decreased absorption of magnesium (e.g., Crohn disease, ETOH abuse) No patients who have diarrhea where magnesium might make it worse (per provider discretion) PRIOR CONCURRENT THERAPY: None of the following current (≤ 28 days prior to registration) or planned therapies (tamoxifen, raloxifene, or aromatase inhibitors are allowed, but the patient must have been on a constant dose for ≥ 28 days and must not be expected to stop the medication during the study period): Antineoplastic chemotherapy (trastuzumab or lapatinib are allowed) Androgens Estrogens (any delivery route) Progestational agents No prior use of magnesium for hot flashes No current or planned use of gabapentin (for any reasons) or antidepressants (for any reasons) or other agents for treating hot flashes (except stable dose of vitamin E is allowed as long as it was started > 30 days prior to study registration and are to be continued through the study period; soy is allowed, if it is planned to be continued at the same dose during the study period) No current use of magnesium for any indication (except one standard multiple vitamin dose is allowed per day) Not taking diuretics, corticosteroids, bile acid sequestrants, and other prescription and over-the-counter medications that may affect magnesium levels No current (≤ 7 days prior to registration) or planned use of other non-drug therapies for managing hot flashes, such as acupuncture or yoga (use of these therapies for other reasons is allowed)

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive a low-dose of magnesium oxide orally (PO) daily (QD). | Drug: magnesium oxide<br>* Given PO<br>|
| Experimental: Arm II<br>Patients receive a high-dose of magnesium oxide PO QD. | Drug: magnesium oxide<br>* Given PO<br>|
| Placebo Comparator: Arm III<br>Patients receive a low-dose of placebo PO QD. | Other: placebo<br>* Given PO<br>|
| Placebo Comparator: Arm IV<br>Patients receive a high-dose of placebo PO QD. | Other: placebo<br>* Given PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Intra-patient Changes of Weekly Hot Flash Activity From Baseline During the Treatment Period. | The primary endpoint is the intra-patient changes of weekly hot flash activity from baseline during the treatment period. The hot flash activity will be measured by the weekly average hot flash score, which is a composite entity of both frequency and severity of hot flashes. The hot flash severity is graded from 1 to 4 (1=mild, 2=moderate, 3=severe, and 4=very severe). The daily hot flash score is computed by multiplying the mean grade of severity by the frequency during every 24 hour period. Therefore, a score of zero is the lowest possible score and can be interpreted as having no hot flashes. The weekly hot flash score was calculated by adding all scores for the week. The mean Hot Flash Score for each week for each group is reported and a repeated measures analysis is reported comparing each dose level group to the Placebo group. | Baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly Frequency of Hot Flashes as Measured by the Hot Flash Diary During the Treatment Period | As part of the Hot Flash Diary, the number of hot flashes was recorded for each patient for each week. For this endpoint, the mean number of hot flashes for each group is reported. A repeated measure analysis comparing each dose level group and the Placebo is reported. | Baseline to Week 8 | 
| Frequency and Maximum Grade of Adverse Events Reported Via the CTCAE 4.0 During the Treatment Period. | Frequency and severity of adverse events reported by patients in weekly Symptom Experience Questionnaire and evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report. | Baseline to Week 8 | 
| The Change of Severity of Symptoms as Measured the Symptom Experience Questionnaire From Baseline to Treatment Termination | We will use the Symptom Experience Questionnaire (SEQ) 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. The questionnaire is 14 questions and is based on a 0=Not at all to 10=As bad as it can be scale. The change of severity of symptoms as measured by the SEQ from baseline to treatment termination will be first summarized by descriptive statistics as a percent change from baseline. | Baseline to week 8 | 
| The Change of Daily Interference as Measured by the Hot Flash Related Daily Interference Scale (HFRDIS) From Baseline to Treatment Termination. | We will use the Hot Flash Related Daily Interference Scale (HFRDIS) (SEQ) to evaluate the specific effect of hot flashes have on various life activities such as work, social, leisure and relationships while receiving treatment. The questionnaire is 10 questions and is based on a 0=Do not interfere to 10=Completely interfere scale. The weekly score is the summation of these 10 questions and therefore ranges from 0 to 100. The total change in severity of symptoms is calculated by subtracting the week 8 score from the baseline. Therefore, values below zero indicate a worsening of symptoms and values above zero indicate an improvement and has a maximum range of -100 to 100. A gatekeeper procedure, following a fixed-sequence hypothesis testing method, was used to examine the higher dose of magnesium vs. placebo first and then the lower dose of magnesium vs. placebo, if the former was statistically significant. | Baseline to week 8 | 
| The Intra-patient Changes of Magnesium Level From Baseline to the End of Treatment Period Between Magnesium Oxide and Placebo Arms. | The intra-patient changes of magnesium level from baseline to the end of treatment period between magnesium oxide and placebo arms will be compared using a repeated measures model. Serum magnesium concentrations will be performed prior to study medication usage and during the last week of blinded study use. These will be obtained in the first 150 patients. Mean change in serum magnesium concentrations will be compared between the 3 study arms to determine whether there are any apparent changes in the patients receiving placebos vs the two magnesium doses. | Baseline to week 8 | 

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