Breast Cancer, Hot Flashes
Conditions
Keywords
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, hot flashes
Brief summary
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
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.
Interventions
DRUGSt. John's Wort
St. John's Wort 300mg tablet three times per day
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of St. John's Wort on Hot Flash Frequency as Recorded in a Daily Hot Flash Diary From Baseline to 4 Weeks | Baseline and four weeks | Primary objective was to assess the change in hot flashes over a four week period in patients given St. John's Wort |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of St. John's Wort on Hot Flash Score as Recorded in a Daily Hot Flash Diary From Baseline to 4 Weeks | Baseline and four 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. |
| Estimation of Toxicities While on St. John's Wort | Six weeks following baseline (four weeks of active treatment and two weeks of follow-up) | 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. |
| Effect of St. John's Wort on Quality of Life (MCS) | Baseline and four weeks | 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. |
| Effect of St. John's Wort on Quality of Life (PCS) | Baseline and four weeks | 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. |
| Mood is Measured by the POMS Short Form. | Baseline and four weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| St. John's Wort Patient given one 300mg St. John's Wort tablet three times per day
St. John's Wort: St. John's Wort 300mg tablet three times per day | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | St. John's Wort |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 55.2 years STANDARD_DEVIATION 7 |
| Race/Ethnicity, Customized White | 9 participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
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
Time frame: Baseline and four weeks
Population: All registered participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| St. John's Wort | Effect of St. John's Wort on Hot Flash Frequency as Recorded in a Daily Hot Flash Diary From Baseline to 4 Weeks | Baseline | 7.8 number of occurrences | Standard Deviation 5.3 |
| St. John's Wort | Effect of St. John's Wort on Hot Flash Frequency as Recorded in a Daily Hot Flash Diary From Baseline to 4 Weeks | Four Weeks | 7.0 number of occurrences | Standard Deviation 5.3 |
Comparison: Analysis of the change in hot flash frequency from baseline to four weeks; null hypothesis is no change.p-value: 0.262995% CI: [-2.36, 0.74]paired t-test
Secondary
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.
Time frame: Baseline and four weeks
Population: All registered participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| St. John's Wort | Effect of St. John's Wort on Hot Flash Score as Recorded in a Daily Hot Flash Diary From Baseline to 4 Weeks | Baseline | 19.4 frequency times severity | Standard Deviation 17.5 |
| St. John's Wort | Effect of St. John's Wort on Hot Flash Score as Recorded in a Daily Hot Flash Diary From Baseline to 4 Weeks | Four Weeks | 15.0 frequency times severity | Standard Deviation 17.3 |
Comparison: Assessment of the change in the hot flash score over timep-value: 0.136595% CI: [-10.45, 1.72]paired t-test
Secondary
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.
Time frame: Baseline and four weeks
Population: All registered participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| St. John's Wort | Effect of St. John's Wort on Quality of Life (MCS) | Baseline | 53.3 units on a scale | Standard Deviation 7.5 |
| St. John's Wort | Effect of St. John's Wort on Quality of Life (MCS) | Four Weeks | 53.8 units on a scale | Standard Deviation 4 |
Comparison: Assess the change in MCS from baseline to four weeks in patients receiving St. John's wort.p-value: 0.83295% CI: [-4.84, 5.92]paired t-test
Secondary
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.
Time frame: Baseline and four weeks
Population: All registered participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| St. John's Wort | Effect of St. John's Wort on Quality of Life (PCS) | Baseline | 47.4 units on a scale | Standard Deviation 12.6 |
| St. John's Wort | Effect of St. John's Wort on Quality of Life (PCS) | Four Weeks | 47.4 units on a scale | Standard Deviation 9.6 |
Comparison: Assess the change in PCS from baseline to four weeks; null hypothesis is no change.p-value: 0.999595% CI: [-5.71, 5.71]paired t-test
Secondary
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.
Time frame: Six weeks following baseline (four weeks of active treatment and two weeks of follow-up)
Population: All registered participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| St. John's Wort | Estimation of Toxicities While on St. John's Wort | 66.67 percentage of participants |
Secondary
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.
Time frame: Baseline and four weeks
Population: All registered participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| St. John's Wort | Mood is Measured by the POMS Short Form. | Baseline | 51.7 units on a scale | Standard Deviation 8.4 |
| St. John's Wort | Mood is Measured by the POMS Short Form. | Four Weeks | 56.1 units on a scale | Standard Deviation 3.4 |
Comparison: Assess the change in mood from baseline to four weeks. Null hypothesis is no change.p-value: 0.104295% CI: [-1.12, 9.822]paired t-test