Reishi Mushroom Extract for Fatigue and/or Arthralgias/Myalgias in Patients With Breast Cancer on Aromatase Inhibitors

Study Overview
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Brief Summary
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This phase II trial tests how well Reishi mushroom extract works in treating fatigue and/or joint/muscle pain (arthralgias/myalgias) in patients with breast cancer on aromatase inhibitors. Fatigue and arthralgias/myalgias are common symptoms in breast cancer patients taking aromatase inhibitors (AI). Given the long duration of AI treatment for some women (up to 10 years), these symptoms can significantly impact quality of life and premature discontinuation of AIs, a beneficial medication. Reishi mushrooms are among several medicinal mushrooms that have been used for hundreds of years, mainly in Asian countries, to help enhance the immune system, reduce stress, improve sleep, and lessen fatigue. Reishi mushroom extracts have not been studied explicitly for treatment-induced arthralgias/myalgias, but have been shown to improve quality of life, muscular strength, pain, and flexibility. Information from this study may help researchers determine the effect of Reishi mushroom extract on fatigue and arthralgias/myalgias in breast cancer patients receiving an AI.

Detailed Description
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PRIMARY OBJECTIVE: I. To evaluate the efficacy of 1,000 mg three times daily (TID) of Reishi mushroom extracts as therapy for cancer-related fatigue measured by uniscale measurement at the end of four weeks. SECONDARY OBJECTIVES: I. To evaluate the efficacy of Reishi mushroom extracts as therapy for cancer-related arthralgias at the end of four weeks and four weeks after cross-over as measured by the Brief Pain index (BPI)-adapted for AI associated arthralgias. II. To evaluate the effect of Reishi mushroom extracts on cancer-related quality of life (QOL), as measured by uniscale, at the end of four weeks and four weeks after cross-over. III. To evaluate the efficacy of Reishi mushroom extracts on mood, as assessed by the World Health Organization Five Well-Being Index (WHO-5) item well-being scale, at the end of four weeks and four weeks after cross-over. IV. To evaluate treatment toxicity between the two treatment arms, as measured by a patient symptom experience diary and weekly calls from the study team. V. To evaluate the interest, knowledge, and acceptance of integrative treatments for cancer-related symptoms. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive Reishi mushroom extract orally (PO) TID on days 1-28 for weeks 1-4 and then placebo PO TID on days 1-28 for weeks 5-8 in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO TID on days 1-28 for weeks 1-4 and Reishi mushroom extract PO TID on days 1-28 for weeks 5-8 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.

Official Title
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Reishi Mushroom Extract for Fatigue and/or Arthralgias in Patients With Breast Cancer on Aromatase Inhibitors: A Randomized Phase II MNCCTN Trial

Conditions
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Estrogen Receptor-Positive Breast Carcinoma

Intervention / Treatment
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* Dietary Supplement: Mushroom
* Drug: Placebo Administration
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years History of breast cancer, estrogen receptor positive (ER+), Her 2 positive or negative Fatigue ≥ 4/10 Currently taking any aromatase inhibitor in the curative setting and planning to be on such for at least 8 weeks after registration. (Patients on concurrent ovarian suppression [such as with leuprolide acetate, goserelin] are allowed) Prior treatment: last chemotherapy ≥ 90 days prior to randomization (if treated with chemotherapy) On a stable dose of pain medications if pain medications are being regularly used. (i.e., no change in dosage in the past 30 days) If on supplements, must be on stable dose with no plan to change; not on or planning any acupuncture or other specific supportive modalities for fatigue or AI arthralgias Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 White blood cell count (WBC) ≥ 3,000/mm^3 (obtained ≤ 30 days prior to randomization) Hemoglobin ≥ 10 g/dL (obtained ≤ 30 days prior to randomization) Platelet count ≥ 100,000/mm^3 (obtained ≤ 30 days prior to randomization) Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 30 days prior to randomization) Alanine aminotransferase (ALT) or aspartate transaminase (AST) ≤ 1.2 x ULN (obtained ≤ 30 days prior to randomization) Prothrombin time (PT)/activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (obtained ≤ 30 days prior to randomization) Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only Provide written informed consent Ability to complete questionnaires Willing to return to enrolling institution during the active monitoring phase of the study Exclusion Criteria: Other known uncontrolled medical conditions causing fatigue such as untreated thyroid disease, depression, fibromyalgia, chronic fatigue syndrome, infection, autoimmune disease, or active/untreated hepatitis Allergy to mushrooms On anticoagulation medication or aspirin or having a known bleeding disorder On any specific medication for fatigue (e.g., methylphenidate) Metastatic cancer diagnosis (history of nodal metastases is allowed) Chronic steroid use, unless on physiologic replacement doses Current use of any medical mushrooms On medications for diabetes History of symptomatic hypotension Taking CYP3A4, CYP2D6 or CYP2E1 substrates Taking CDK4/6 inhibitors or olaparib Any of the following because this study involves an agent that has unknown genotoxic, mutagenic and teratogenic effects: Pregnant persons Nursing persons Persons of childbearing potential who are unwilling to employ adequate contraception

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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (Reishi mushroom extract, placebo)<br>Patients receive Reishi mushroom extract PO TID on days 1-28 for weeks 1-4 and then placebo PO TID on days 1-28 for weeks 5-8 in the absence of disease progression or unacceptable toxicity. | Dietary Supplement: Mushroom<br>* Given Reishi mushroom extract PO<br>* Other names: CULTIVATED MUSHROOM;Drug: Placebo Administration<br>* Given PO<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm II (placebo, Reishi mushroom extract)<br>Patients receive placebo PO TID on days 1-28 for weeks 1-4 and Reishi mushroom extract PO TID on days 1-28 for weeks 5-8 in the absence of disease progression or unacceptable toxicity. | Dietary Supplement: Mushroom<br>* Given Reishi mushroom extract PO<br>* Other names: CULTIVATED MUSHROOM;Drug: Placebo Administration<br>* Given PO<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fatigue scores | Based on a single item fatigue uniscale question. Will be compared between arms using a two-sided two-sample t-test assuming equal variances in each group. | Baseline to end of four weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quality of life | Measured by the World Health Organization-Five Well-Being Index. Will be compared between arms using two-sample, two-sided t-tests assuming equal variances and alpha levels of 5%. The analyses of the crossover portion of the study will be descriptive. Mean values will be plotted over time by arm. A formal crossover analysis will also be performed using Senn's linear modeling approach. | Baseline to the end of four weeks and four weeks after cross-over | 
| Change in arthralgias | Measured by the Brief Pain Inventory for Aromatase Inhibitor Induced Arthralgia. Will be compared between arms using two-sample, two-sided t-tests assuming equal variances and alpha levels of 5%. The analyses of the crossover portion of the study will be descriptive. Mean values will be plotted over time by arm. A formal crossover analysis will also be performed using Senn's linear modeling approach. | Baseline to the end of four weeks and four weeks after cross-over | 
| Incidence of adverse events | Measured by the symptom experience diary. Will be compared between arms using two-sample, two-sided t-tests assuming equal variances and alpha levels of 5%. The analyses of the crossover portion of the study will be descriptive. Mean values will be plotted over time by arm. A formal crossover analysis will also be performed using Senn's linear modeling approach. | Up to 30 days follow-up |