Acupuncture in Reducing Muscle and Bone Symptoms in Women Receiving Letrozole, Exemestane, or Anastrozole for Stage 0, Stage I, Stage II, or Stage III Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Acupuncture may help relieve muscle and bone pain caused by aromatase inhibitor therapy, such as letrozole, exemestane, and anastrozole. PURPOSE: This randomized phase II trial is studying acupuncture to see how well it works in reducing muscle and bone symptoms in women receiving letrozole, exemestane, or anastrozole for stage 0, stage I, stage II, or stage III breast cancer.

Detailed Description
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OBJECTIVES: Primary To determine if acupuncture can reduce aromatase inhibitor (AI)-associated musculoskeletal symptom severity, in terms of function and pain, in woman with stage 0-III breast cancer. Secondary To assess if acupuncture decreases oral analgesic use in these patients. To assess if acupuncture decreases the proportion of patients who change or discontinue AI therapy. To assess if acupuncture improves menopausal symptoms, mood (i.e., depression or anxiety), sleep quality and sleep disturbance, and overall quality of life of these patients. To assess if acupuncture changes plasma concentrations of estrogens (i.e., E1, E2, and E1S), cytokine profile, and beta endorphin. OUTLINE: This is a multicenter study. Patients are stratified according to participation in the aromatase inhibitor trial, A Multicenter Randomized Clinical Trial Correlating the Effects of 24 Months of Exemestane or Letrozole on Surrogate Markers of Response With Aromatase Polymorphism (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I (control): Patients receive 8 weekly sessions of sham acupuncture treatment comprising 20 minutes of a non-penetrating device consisting of a retractable needle and an adhesive tube on the skin using the Park Sham Device (PSD) in 14 non-acupuncture points. Patients may receive 4 free acupuncture sessions (not sham) after the 12-week (previously 24-week) follow-up visit. Arm II (treatment): Patients receive 8 weekly sessions of acupuncture treatment comprising 20 minutes of needle insertion in 15 acupuncture points including CV 4, CV 6, CV12 and bilateral LI 4, MH 6, GB 34, ST 36, KI 3, BL 65. Quality of life is assessed periodically to measure changes in symptoms that may be related to hot flashes and estrogen deprivation (i.e., menopausal symptoms, mood [depression and anxiety], sleep quality, and overall quality of life using the menopausal symptoms checklist); the Hot Flash Related Daily Interference Scale (HFRDI) and the Hot Flash Daily Diary; the Pittsburgh Sleep Quality Index (PSQI); the Center for Epidemiologic Studies Depression Scale (CESD); the Hospital Anxiety and Depression Scale (HADS-A); and the EuroQOL. Patients complete questionnaires including the Health Assessment Questionnaire (HAQ) and visual analog scales (VAS) to assess both pain and global health status at baseline, after 4 and 8 weeks of acupuncture or sham acupuncture, and at follow-up at 12 weeks (previously 24 weeks). The average amount of daily oral analgesic usage is assessed at weeks 0, 4, 8, and 12(previously 24). Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for plasma concentrations of estrogen (i.e., estrone E1, estradiol E2, and estrone sulfate E1S) via HPLC-MS/MS, level of 35 serum cytokines via addressable laser bead immunoassay (ALBIA) or classical sandwich ELISA, cytokines and their soluble receptors via classical sandwich ELISA techniques, and Beta-endorphin via competitive ELISA. All patients are followed for 12 weeks(previously 24 weeks). Patients in arm I may be followed for an additional 4 weeks if they choose to receive the free acupuncture sessions.

Official Title
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A Multi-Center Randomized Controlled Double Blind Trial Assessing the Effect of Acupuncture in Reducing Musculoskeletal Symptoms in Breast Cancer Patients Taking Aromatase Inhibitors

Conditions
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Anxiety Disorder, Breast Cancer, Depression, Fatigue, Hot Flashes, Pain, Sleep Disorders

Intervention / Treatment
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* Procedure: acupuncture therapy
* Procedure: sham intervention


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed invasive carcinoma of the breast Stage 0-III disease Estrogen receptor- and/or progesterone receptor-positive by immunohistochemical staining Must be receiving a standard dose of aromatase inhibitor (AI) therapy (i.e., letrozole 2.5 mg once daily, exemestane 25 mg once daily, or anastrozole 1 mg once daily) AI therapy has been ongoing for ≥ 1 month and treatment is expected to continue AI-associated musculoskeletal symptoms, defined as ≥ 1 of the following: Physician-confirmed AI-associated musculoskeletal symptoms Patients concurrently enrolled on the clinical trial, A Multi-Center Randomized Clinical Trial Correlating the Effects of 24 Months of Exemestane or Letrozole on Surrogate Markers of Response with Aromatase Polymorphism, and who have met the referral criteria for a rheumatological evaluation No known metastatic (stage IV) breast cancer PATIENT CHARACTERISTICS: ECOG performance status 0-2 Female Menopausal status not specified PRIOR CONCURRENT THERAPY: No prior acupuncture within past 12 months. No other concurrent systemic therapy (i.e., chemotherapy, biologic therapy, or radiotherapy) unless approval is given by the Protocol Chair

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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Arm I (control)<br>Patients receive 8 weekly sessions of sham acupuncture treatment comprising 20 minutes of a non-penetrating device consisting of a retractable needle and an adhesive tube on the skin using the Park Sham Device (PSD) in 14 non-acupuncture points. Patients may receive 4 free acupuncture sessions (not sham) after the 12 or 24-week follow-up visit. | Procedure: sham intervention<br>* Given weekly for 8 sessions<br>* Other names: sham acupuncture;|
| Experimental: Arm II (treatment)<br>Patients receive 8 weekly sessions of acupuncture treatment comprising 20 minutes of needle insertion in 15 acupuncture points including CV 4, CV 6, CV12 and bilateral LI 4, MH 6, GB 34, ST 36, KI 3, BL 65. | Procedure: acupuncture therapy<br>* Given weekly for 8 sessions<br>* Other names: acupuncture;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Assessment Questionnaire Disability Index (HAQ-DI) score |  | Baseline, Weeks 4, 8 and 12 (or Week 24) | 
| Pain scores on visual analog scale (VAS) |  | Baseline, Weeks 4, 8 and 12 (or Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in amount and/or frequency of oral analgesic use |  | Baseline, Weeks 1-8, Week 12 (or Week 24) | 
| Number of patients who discontinue or change AI therapy |  | All timepoints | 
| Change in menopausal symptoms (NSABP-revised), hot flash frequency (HFRDIS), sleep quality (PSQI), depression score (CESD), and overall quality of life (EuroQOL) in patients at weeks 4, 8, and 24 vs week 0 of acupuncture treatment |  | Baseline, Weeks 4, 8 and 12 (or Week 24) | 
| Change in plasma estrogen concentrations, beta endorphin concentration, and cytokine profile from week 0 to week 8 |  | Baseline, Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, fatigue, hot flashes, sleep disorders, depression, anxiety disorder, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer