Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

White Button Mushroom Extract in Preventing the Recurrence of Breast Cancer in Postmenopausal Breast Cancer Survivors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Biomarker/Laboratory analysis, Prevention	Active	21 and over	NCI	CHNMC-07213 07213, NCT00709020

Objectives

Primary

1. To show that a whole food extract of white button mushrooms (WBM) can inhibit aromatase-induced estrogen biosynthesis in postmenopausal women who are breast cancer survivors (BCS).
2. To determine the optimal daily dose of WBM needed to induce aromatase inhibition of estrogen biosynthesis in these patients.
3. To determine the bioavailability of C-18 unsaturated fatty acids, which are thought to moderate the anticancer effects of WBM.

Secondary

1. To determine the safety and tolerability of WBM in humans via serial comprehensive symptom questionnaires, pre- and post-treatment markers of bone metabolism, and pre- and post-treatment comprehensive lipid panels.
2. To explore potential alternate antitumor mechanisms, specifically the effect of WBM on cytokines as well as innate and adaptive cellular immunity.
3. To describe barriers experienced in recruitment of ethnically diverse subjects from the community into a secondary prevention BCS trial utilizing a dietary supplement intervention in an effort to enhance feasibility of a subsequent phase II trial.

Entry Criteria

Disease Characteristics:

• Meets 1 of the following criteria:
  • Prior diagnosis of infiltrating carcinoma of the breast ≥ 5 years prior to study entry
  • Prior diagnosis of ductal carcinoma in situ



• No evidence of disease



• Completed all cancer therapy, with the exception of reconstructive surgery, at least 6 months prior to study entry



• Meets one of the following criteria:
  • Normal mammogram within 1 year of study entry
  • Underwent bilateral mastectomy and has been in remission for 5 years, as documented by an oncologist



• Hormone receptor status not specified

Prior/Concurrent Therapy:

• See Disease Characteristics
• More than 3 months since prior and no concurrent hormone-modifying medications, including any of the following:
  • Oral contraceptives
  • Hormone replacement
  • Selective estrogen receptor modifiers
  • Other aromatase inhibitors
  • Gonadotropic-releasing hormone modifiers
• At least 1 month since prior and no other concurrent mushroom extracts or DHEA as a dietary supplement
• No concurrent therapy, except continued medications for unrelated illness that are not excluded, and necessary medications for unrelated acute illnesses that may occur during the study (e.g., cold, flu, or infection)
• No more than 3 concurrent servings per week of the following foods:
  • Flaxseeds and flaxseed meal
  • High-energy bars or diet bars containing soy or soy protein
  • Liquid-nutrition drinks containing soy or soy protein (e.g., Odwalla Future Shake or Ensure Plus)
  • Miso soup
  • Natto
  • Packaged mixed dishes with soy or tofu (e.g., lasagna, burritos, or stir-fry)
  • Cooked soybeans or edamame (i.e., green soybeans)
  • Roasted soy nuts
  • Soymilk, regular or low-fat, plain or flavored
  • Soy cheese, such as cheddar, mozzarella, cram cheese, or parmesan (includes all foods made with soy cheese)
  • Soy protein powders (e.g., performance or body-builder powders)
  • Soy yogurt, all types
  • Soy sauce, tamari, teriyaki sauce, Szechuan sauce, or hoisin sauce
  • Soy ice cream, tofutti, or other soy desserts
  • Tempeh, all types
  • Tofu, all types, including low-fat, flavored, marinated, and smoked
  • Tofu or soy breakfast sausage, bacon, or other breakfast meat
  • Tofu or soy cold cuts, hot dogs, or other deli meat substitutes
  • Veggie soy or tofu burger, ground meat substitute (texturized vegetable protein), or soy or tofu, chicken, or turkey
• Concurrent supplemental calcium and/or vitamin D and bisphosphonates allowed provided doses remain constant throughout the run-in and treatment portions of the trial

Patient Characteristics:

• ECOG performance status 0-1
• WBC ≥ 3,500/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9.0 g/dL
• Postmenopausal, defined as any of the following:
  • Continuous absence of menstruation for 12+ months
  • Status post bilateral oophorectomy
  • Status post hysterectomy with follicle-stimulating hormone in menopausal range
• Creatinine ≤ 1.5 times upper limit of normal (ULN) or less
• Total bilirubin ≤ 1.5 times ULN
• AST and ALT < 2 times ULN
• No allergy to mushrooms
• No personal history of any invasive cancer, other than breast cancer, or squamous cell or basal cell skin cancer
• No osteoporosis, defined as a bone-mineral density T-score of < -2.5 on dual-energy x-ray absorptiometry scan
• No major systemic infections or other major medical illnesses of the cardiovascular, respiratory, or digestive system

Expected Enrollment

Outcomes

Efficacy of white button mushroom extract (WBM) in reducing serum estradiol (E2)
Serum sex steroid hormone levels
Optimal daily dose of WBM
Pharmacokinetics of C-18 unsaturated fatty acids (CUFA) as measured by high-performance liquid chromatography tandem-mass spectrometry
Pharmacodynamics of WBM as measured by ex vivo plasma aromatase inhibition assays

Safety and tolerability of WBM as assessed by NCI CTCAE v3.0, symptom logs, bone metabolism markers, and pre- and post-treatment comprehensive lipid panels
Effect of WBM on cytokines as measured by multiplex cytokine analyses
Effect of WBM on innate and adaptive cellular immunity as measured by immunologic assays
Barriers to recruitment of ethnically diverse patients from the community
Dietary sources of CUFA as measured by food frequency questionnaires
Bone metabolism markers (i.e., serum procollagen type-1 propeptide and urine N-telopeptide crosslinks)
Fasting lipids (i.e., total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides)

Outline

This is a dose-escalation study.

Patients receive oral white button mushroom extract twice daily for 12 weeks in the absence of a second primary ductal carcinoma in situ, invasive breast cancer, or unacceptable toxicity.

Patients undergo blood and urine sample collection at baseline and periodically during treatment for pharmacokinetic, pharmacodynamic, and immunologic correlative studies. Blood and urine samples are analyzed for concentrations of C-18 unsaturated fatty acids (CUFA) by high-performance liquid chromatography tandem-mass spectrometry. Blood samples are also analyzed for anti-aromatase activity by ex vivo plasma aromatase inhibition assays; circulating sex steroid hormones by radioimmunoassay; serum immune cytokine levels by multiplex cytokine analyses; immunophenotyping, NK-cell activation status, and NK-cell function by multiparameter flow cytometry; lipid levels by lipid assays; and biochemical markers of bone metabolism by bone metabolism marker assays. DNA, RNA, and plasma samples are stored for post-trial pharmacogenomic studies.

Trial Contact Information

Trial Lead Organizations

City of Hope Comprehensive Cancer Center

Melanie Palomares, MD, MS, Principal investigator		Ph: 626-256-8662; 800-826-4673

U.S.A.
California
	Duarte
	City of Hope Comprehensive Cancer Center
		Melanie Palomares, MD, MS	Ph:  800-826-4673
			Email: mpalomares@coh.org
	Pasadena
	City of Hope Medical Group
		Steven Kohler, MD	Ph:  626-396-2900

Registry Information
Official Title		A Translational Breast Cancer Prevention Trial of Mushroom Powder in Postmenopausal Breast Cancer Survivors
Trial Start Date		2008-06-16
Trial Completion Date		2011-06-16 (estimated)
Registered in ClinicalTrials.gov		NCT00709020
Date Submitted to PDQ		2008-06-20
Information Last Verified		2008-12-07
NCI Grant/Contract Number		CA33572