Clinical trial NCT06028022: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Estrogen Receptor-Positive Breast Carcinoma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2023-09-07
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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

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)

Primary outcomes:
measure: Change in fatigue scores
timeFrame: Baseline to end of four weeks
Secondary outcomes:
measure: Change in quality of life
timeFrame: Baseline to the end of four weeks and four weeks after cross-over
measure: Change in arthralgias
timeFrame: Baseline to the end of four weeks and four weeks after cross-over
measure: Incidence of adverse events
timeFrame: Up to 30 days follow-up
Other outcomes:
Locations:
city: Albert Lea
country: United States
facility: Mayo Clinic Health System in Albert Lea
state: Minnesota
city: Baxter
country: United States
facility: Essentia Health Baxter Clinic
state: Minnesota
city: Bemidji
country: United States
facility: Sanford Joe Lueken Cancer Center
state: Minnesota
city: Brainerd
country: United States
facility: Essentia Health Saint Joseph's Medical Center
state: Minnesota
city: Deer River
country: United States
facility: Essentia Health Deer River Clinic
state: Minnesota
city: Detroit Lakes
country: United States
facility: Essentia Health Saint Mary's - Detroit Lakes Clinic
state: Minnesota
city: Duluth
country: United States
facility: Essentia Health Cancer Center
state: Minnesota
city: Ely
country: United States
facility: Essentia Health Ely Clinic
state: Minnesota
city: Fosston
country: United States
facility: Essentia Health Fosston
state: Minnesota
city: Hibbing
country: United States
facility: Essentia Health Hibbing Clinic
state: Minnesota
city: International Falls
country: United States
facility: Essentia Health International Falls Clinic
state: Minnesota
city: Mankato
country: United States
facility: Mayo Clinic Health Systems-Mankato
state: Minnesota
city: Monticello
country: United States
facility: MMCORC CentraCare Monticello Cancer Center
state: Minnesota
city: Moose Lake
country: United States
facility: Essentia Health Moose Lake
state: Minnesota
city: Park Rapids
country: United States
facility: Essentia Health Park Rapids
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Sandstone
country: United States
facility: Essentia Health Sandstone
state: Minnesota
city: Thief River Falls
country: United States
facility: Sanford Thief River Falls Medical Center
state: Minnesota
city: Virginia
country: United States
facility: Essentia Health Virginia Clinic
state: Minnesota
city: Worthington
country: United States
facility: Sanford Worthington Medical Center
state: Minnesota
Study officials:
affiliation: Mayo Clinic in Rochester
name: Stacy D. D'Andre, MD
role: PRINCIPAL_INVESTIGATOR
References: