St. John's Wort in Relieving Hot Flashes in Postmenopausal Women With Non-Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: St. John's wort may help relieve hot flashes in women with breast cancer. PURPOSE: This phase II trial is studying how well St. John's wort works in relieving hot flashes in women with non-metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the efficacy of Hypericum perforatum (St. John's wort) in alleviating hot flashes, in terms of hot flash frequency, score, and duration and disruption of daily activities caused by hot flashes, in postmenopausal women with non-metastatic breast cancer. Determine hot flash changes over 4 weeks in patients treated with this drug. Secondary Determine the toxicity of this drug in these patients. Determine the effect of Hypericum perforatum (St. John's wort) on serum tamoxifen levels in women receiving tamoxifen therapy. Determine the effect of Hypericum perforatum (St. John's wort) on general health-related quality of life and mood at 2 and 4 weeks relative to baseline, and during the 2 week post-treatment phase in these patients. To evaluate changes in average weekly hot flush scores and duration over course of study. OUTLINE: This is a multicenter study. Patients receive oral Hypericum perforatum (St. John's wort) three times daily for 4 weeks in the absence of disease progression or unacceptable toxicity. Patients complete a daily diary of the frequency, severity, and duration of their hot flashes, and complete quality of life and mood assessments every 2 weeks during study treatment and continuing weekly for 2 weeks after completion of study treatment. Patients receiving tamoxifen will have blood tests to measure serum tamoxifen levels at baseline, 2, 4, and 6 weeks. PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study.

Official Title
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A Phase II Study of St. John's Wort for the Treatment of Hot Flashes in Women With a History of Breast Cancer

Conditions
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Breast Cancer, Hot Flashes

Intervention / Treatment
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* Drug: St. John's Wort


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: Noninvasive ductal carcinoma in situ Localized breast cancer Stage 0-IIIB disease Locally recurrent breast cancer that is post-treatment AND disease-free for ≥ 2 years Experiencing ≥ 3 hot flashes per day (≥ 21 per week), defined by sweating, flushing, sensation of warmth, night sweats, and/or rapid heart beat of sufficient severity that the patient desires therapeutic intervention Normal mammogram within the past 10 months Hormone receptor status: Not specified INCLUSION CRITERIA: Age 18 and over Sex Female Menopausal status Post-menopausal (i.e., no menstrual periods ≥ 12 months or surgical menopause) Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin < 2 mg/dL SGOT ≤ 2 times normal Renal Not specified EXCLUSION CRITERIA: Not pregnant or nursing Fertile patients must use effective contraception No history of intolerance to St. John's wort PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No concurrent cytotoxic chemotherapy Endocrine therapy No concurrent selective estrogen-receptor modulators or aromatase inhibitors (e.g., anastrozole, letrozole, or exemestane) allowed Concurrent tamoxifen allowed No concurrent estrogen, progestational agents, or androgens for the alleviation of hot flashes No concurrent corticosteroids Radiotherapy Not specified Surgery Not specified Other More than 14 days since prior Hypericum perforatum (St. John's wort), monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (e.g., sertraline, paroxetine, or fluoxetine) or selective norepinephrine reuptake inhibitors (e.g., venlafaxine) No concurrent use of any of the following: Antidepressants Theophylline Warfarin, unless for central line prophylaxis Protease inhibitors for AIDS Digoxin Cyclosporine Benzodiazepines (e.g., diazepam or alprazolam) Calcium-channel blockers (e.g., diltiazem or nifedipine) Coenzyme A reductase inhibitors for serum cholesterol reduction Macrolide antibiotics (e.g., azithromycin, erythromycin, or clarithromycin) Griseofulvin Phenobarbital Phenytoin Rifampin Rifabutin Grapefruit juice Other naturopathic or herbal products Ketoconazole Fluconazole Itraconazole Rifabutin No other concurrent medications for the alleviation of hot flashes (e.g., clonidine or bellamine)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: St. John's Wort<br>Patient given one 300mg St. John's Wort tablet three times per day | Drug: St. John's Wort<br>* St. John's Wort 300mg tablet three times per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of St. John's Wort on Hot Flash Frequency as Recorded in a Daily Hot Flash Diary From Baseline to 4 Weeks | Primary objective was to assess the change in hot flashes over a four week period in patients given St. John's Wort | Baseline and four weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of St. John's Wort on Hot Flash Score as Recorded in a Daily Hot Flash Diary From Baseline to 4 Weeks | The hot flash score is calculated as the frequency of hot flashes times the severity of the hot flashes averaged over a week. Frequency is the number of hot flashes in a day. Severity is coded 0=None, 1=Mild, 2=Moderate, and 3=Severe. Score for each day is frequency times severity. Weekly score is averaged over seven days. Score ranges from 0 to infinity Lower scores are better. | Baseline and four weeks | 
| Estimation of Toxicities While on St. John's Wort | Toxicities are quantified using the standard NCI toxicity criteria. The outcome is the percentage of participants who experience one or more toxicities. More detailed information on toxicities is found in the adverse events section. | Six weeks following baseline (four weeks of active treatment and two weeks of follow-up) | 
| Effect of St. John's Wort on Quality of Life (MCS) | Quality of life was measured by the SF12 (MCS and PCS subscales). First we'll summarize the MCS. SF-12 is the short form Health Survey (a short version of the SF-36) developed for the Medical Outcomes Study. It is managed by QualityMetric. MCS is the mental health component of the SF-12. A normal population has a mean of 50 and a SD of 10. Higher numbers represent better mental health. The range is 0 to 100. Higher scores represent better mental health. | Baseline and four weeks | 
| Effect of St. John's Wort on Quality of Life (PCS) | Quality of life was measured by the SF12 (MCS and PCS subscales). Now we'll summarize the PCS. SF-12 is the short form Health Survey (a short version of the SF-36) developed for the Medical Outcomes Study. It is managed by QualityMetric. PCS is the physical health component of the SF-12. Normal population has a mean of 50 and a SD of 10. Higher scores reflect better physical health. The range is 0 to 100. Higher scores represent better mental health. | Baseline and four weeks | 
| Mood is Measured by the POMS Short Form. | POMS stands for the Profile of Mood States This is a short version of the POMS (17 questions). Each question is scored on a 0 to 4 scale. The POMS score is the sum of the responses to the 17 questions. Responses to some questions have been reversed to make higher responses better. The range is 0 to 68. Higher scores represent better overall mood. | Baseline and four weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hot flashes, recurrent breast cancer, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, breast cancer in situ, ductal breast carcinoma in situ