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

Official title

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

Overview

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

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.

Interventions

• Dietary supplement Mushroom Extract
  Given Reishi mushroom extract PO
• Drug Placebo Administration
  Given PO
• Other Quality-of-Life Assessment
  Ancillary studies
• Other Questionnaire Administration
  Ancillary studies

Primary outcome measures

• Change in fatigue scores [Time frame: Baseline to end of four weeks]

Secondary outcome measures (3)

• Change in quality of life [Time frame: Baseline to the end of four weeks and four weeks after cross-over]
• Change in arthralgias [Time frame: Baseline to the end of four weeks and four weeks after cross-over]
• Incidence of adverse events [Time frame: Up to 30 days follow-up]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• History of breast cancer, estrogen receptor positive (ER+), Her 2 positive or negative
• Fatigue ≥ 4/10
• Currently post-menopausal (as defined by National Comprehensive Cancer Network (version 4.2024), taking any aromatase inhibitor in the curative setting and planning to be on such for at least 8 weeks after registration. \[Patients on concurrent ovarian suppression (such as with leuprolide acetate, goserelin) are allowed\]; CDK 4/6 inhibitors abemaciclib, ribociclib 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 on concurrent ovarian suppression only
• Provide informed consent
• Ability to complete questionnaires
• Willing to return to enrolling institution during the active monitoring phase of the study
• Patients who have had a recent surgery or procedure should be healed and cleared by their clinician and/or surgeon per local standards, prior to registration

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 sensitive substrates which can be located at the following link:

https://www.fda.gov/drugs/drug-interactions-labeling/healthcare-professionals-fdas-examples-drugs-interact-cyp-enzymes-and-transporter-systems

• Drugs which exhibit either >20% inhibition or >20% induction of CYP2E1 in vivo, such as: Acetaminophen, Dapsone, Enflurane, Halothane, Isoflurane, \& Theophylline
• Taking olaparib
• Any of the following because this study involves an agent that has unknown genotoxic, mutagenic and teratogenic effects:

• Pregnant persons
• Nursing persons
• Persons on concurrent ovarian suppression who are unwilling to employ adequate contraception (e.g., hormonal methods, barrier methods, intrauterine device, abstinence)
• Planned surgery or procedure during time on study and ≤ 14 days after last dose, due to bleeding risks

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Supportive care

Study locations

United States · 23 centers

• Mayo Clinic Health System in Albert Lea — Albert Lea
• Essentia Health Baxter Clinic — Baxter
• Sanford Joe Lueken Cancer Center — Bemidji
• Essentia Health Saint Joseph's Medical Center — Brainerd
• Essentia Health Deer River Clinic — Deer River
• Essentia Health Saint Mary's - Detroit Lakes Clinic — Detroit Lakes
• Essentia Health Cancer Center — Duluth
• Essentia Health Ely Clinic — Ely
• … and 15 more centers

Identifiers

NCT: NCT06028022 · MC221002 · NCI-2023-06578 · MC221002 · 23-005266 · MNCCTN032

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗