Clinical trial NCT00956813: Flaxseed in Treating Postmenopausal Women With Hot Flashes Who Have a History of Breast Cancer or Other Cancer or Who Do Not Wish to Take Estrogen Therapy
Official title: Phase III, Randomized, Placebo-controlled, Double-Blind Trial of Flaxseed for the Treatment of Hot Flashes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Hot Flashes
Menopausal Symptoms
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: menopausal symptoms
hot flashes
breast cancer
unspecified adult solid tumor, protocol specific
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-08-11
Enrollment: 210
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Estrogen can relieve the symptoms of menopause, but can also cause the growth of breast cancer cells. Flaxseed may reduce the number of hot flashes and improve mood and quality of life in postmenopausal women not receiving estrogen therapy.

PURPOSE: This randomized phase III trial is studying flaxseed to see how well it works in treating postmenopausal women with hot flashes who have a history of breast cancer or other cancer or who do not wish to take estrogen therapy.

Detailed description: OBJECTIVES:

* To evaluate the efficacy of flaxseed on hot flash scores in women with a history of breast cancer or other cancer or in women who do not wish to take estrogen therapy for fear of increased risk of breast cancer as measured by a daily prospective hot flash diary.
* To evaluate the side effect profile of flaxseed in this population.
* To evaluate the effects of flaxseed on mood (per the Profile of Mood States) and broader menopausal symptoms (per the MENQOL), daily interference from hot flashes (per the HFRDIS), and perception of benefit (per Global Impression of Change).

OUTLINE: Patients are stratified according to age (18-49 years vs ≥ 50 years); treatment with tamoxifen citrate, selective estrogen receptor modulators, or aromatase inhibitors (yes vs no); duration of hot flashes (≤ 9 months vs \> 9 months); and daily frequency of hot flashes (4-9 vs ≥ 10). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral flaxseed in the form of a bar similar to a granola bar once daily.
* Arm II: Patients receive oral placebo bar once daily. In both arms, treatment continues for 6-12 weeks. Patients in arm II may crossover to receive treatment as in arm I after 6 weeks.

Patients complete questionnaires (Hot Flash Diary, Side Effect Experience Questionnaire, Profile of Mood States, Hot Flash Related Daily Interference Scale, and Menopause Specific Quality of Life) at baseline and periodically during treatment. Patients are contacted by telephone at the end of weeks 2, 4, 5, and 7 to assess product tolerability, document compliance, encourage completion of questionnaires, and address problems.

Eligibility criteria: * Bothersome hot flashes, defined by their occurrence ≥ 28 times per week and of sufficient severity to make the patient desire therapeutic intervention

  * Presence of hot flashes for ≥ 1 month
* Meets 1 of the following criteria:

  * History of breast cancer or other cancer (currently without malignant disease)
  * No history of breast cancer and wishes to avoid estrogen due to a perceived increased risk of breast cancer
* Hormone receptor status not specified
* Postmenopausal as defined by 1 of the following\*:

NOTE: \*Women with ≥ 1 ovary but without a uterus should be deemed postmenopausal by either age \> 55 OR a combination of estrogen within a postmenopausal range (per local lab) and follicle-stimulating hormone \> 40 mIU/mL

* Absence of a period in the past 12 months
* Bilateral oophorectomy

  * ECOG performance status 0-1
  * Life expectancy ≥ 6 months
  * Able to complete questionnaire(s) alone or with assistance
  * No diabetes requiring oral or injectable antihyperglycemics
  * No hypotension
  * No history of allergic or other adverse reaction to flaxseed
  * No irritable bowel syndrome, colitis, Crohn disease, or any gastrointestinal condition where the patient should not consume and/or has an intolerance/allergies to seeds or nuts
  * At least 4 weeks since prior and no concurrent or planned androgens, estrogens, or progestational agents
* Tamoxifen, raloxifene, or aromatase inhibitors are allowed provided the patient has been on a constant dose for ≥ 4 weeks and is not expected to stop the medication during study treatment

  • At least 4 weeks since prior and no concurrent anti-cancer therapies of any kind
* Trastuzumab allowed

  * No concurrent treatment with other anti-cancer therapies of any kind except for trastuzumab or endocrine therapies
  * No concurrent (≤ 7 days prior to registration) or planned use of other agents for treating hot flashes (i.e., gabapentin, clonidine, antidepressants, estrogen treatment, megestrol acetate, or Bellergal)
* Stable dose of vitamin E (as a general vitamin supplement) allowed provided it is ≤ 800 IU/day, it was started \> 30 days before study initiation, and is to be continued through study period
* Patients who have been using antidepressants for mood and have been on a stable dose for over a month and meet the eligibility criteria for hot flash frequency and duration are eligible

  • No concurrent anticoagulants or anti-platelets (1 mg of Coumadin for central line patency allowed)
* Aspirin allowed (≤ 81 mg)

  * No concurrent anti-hypertensives
  * No other concurrent herbal supplements for any reason, including soy and soy supplements (i.e., powders, pills, or milk)

Primary outcomes:
measure: To Evaluate the Efficacy of Flaxseed on Hot Flash Scores in Women as Measured by a Daily Prospective Hot Flash Diary.
timeFrame: Baseline and 7 weeks
Secondary outcomes:
measure: Toxicity as Measured by CTCAE v3.0
timeFrame: Up to 7 weeks
measure: Change of Mood as Measured by the Profile of Mood States (POMS)
timeFrame: Baseline and up to 7 weeks
measure: Change of Menopause Specific Quality of Life as Measured by the Menopause Specific Quality of Life (MENQOL)
timeFrame: Baseline and up to 7 weeks
measure: Change of Daily Interference as Measured by the Hot Flash Related Daily Interference Scale (HFRDIS)
timeFrame: Baseline and up to 7 weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Aurora Presbyterian Hospital
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose Cancer Center at Penrose Hospital
state: Colorado
city: Denver
country: United States
facility: St. Anthony Central Hospital
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - St. Luke's Medical Center
state: Colorado
city: Denver
country: United States
facility: St. Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Grand Junction
country: United States
facility: St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
state: Colorado
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Hope Cancer Care Center at Longmont United Hospital
state: Colorado
city: Loveland
country: United States
facility: McKee Medical Center
state: Colorado
city: Pueblo
country: United States
facility: St. Mary - Corwin Regional Medical Center
state: Colorado
city: Thornton
country: United States
facility: North Suburban Medical Center
state: Colorado
city: Wheat Ridge
country: United States
facility: Exempla Lutheran Medical Center
state: Colorado
city: Hartford
country: United States
facility: Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
state: Connecticut
city: Moline
country: United States
facility: Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
state: Illinois
city: Moline
country: United States
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Elkhart
country: United States
facility: Elkhart Clinic, LLC
state: Indiana
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Kokomo
country: United States
facility: Howard Community Hospital
state: Indiana
city: La Porte
country: United States
facility: Center for Cancer Therapy at LaPorte Hospital and Health Services
state: Indiana
city: Mishawaka
country: United States
facility: Saint Joseph Regional Medical Center
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: South Bend
country: United States
facility: Michiana Hematology-Oncology, PC - South Bend
state: Indiana
city: South Bend
country: United States
facility: South Bend Clinic
state: Indiana
city: Bettendorf
country: United States
state: Iowa
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates - West Des Moines
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Ottumwa
country: United States
facility: McCreery Cancer Center at Ottumwa Regional
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Louisville
country: United States
facility: Drs. Carrol, Sheth, Raghavan
state: Kentucky
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Battle Creek
country: United States
facility: Battle Creek Health System Cancer Care Center
state: Michigan
city: Big Rapids
country: United States
facility: Mecosta County Medical Center
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Escanaba
country: United States
facility: Green Bay Oncology, Limited - Escanaba
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Health Care
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Iron Mountain
country: United States
facility: Dickinson County Healthcare System
state: Michigan
city: Jackson
country: United States
facility: Foote Memorial Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Livonia
country: United States
facility: St. Mary Mercy Hospital
state: Michigan
city: Muskegon
country: United States
facility: Mercy General Health Partners
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Mercy Regional Cancer Center at Mercy Hospital
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute at Saint Mary's - Saginaw
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeside Cancer Specialists, PLLC
state: Michigan
city: St. Joseph
country: United States
facility: Lakeland Regional Cancer Care Center - St. Joseph
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Hospital
state: Michigan
city: Bemidji
country: United States
facility: MeritCare Bemidji
state: Minnesota
city: Fergus Falls
country: United States
facility: Fergus Falls Medical Group, PA
state: Minnesota
city: Mankato
country: United States
facility: Immanuel St. Joseph's
state: Minnesota
city: Fargo
country: United States
facility: CCOP - MeritCare Hospital
state: North Dakota
city: Fargo
country: United States
facility: MeritCare Broadway
state: North Dakota
city: Grand Forks
country: United States
facility: Altru Cancer Center at Altru Hospital
state: North Dakota
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Franklin
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wilmington
country: United States
facility: Clinton Memorial Hospital
state: Ohio
city: Wright-Patterson Afb
country: United States
facility: United States Air Force Medical Center - Wright-Patterson
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Milwaukie
country: United States
facility: Providence Milwaukie Hospital
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Adventist Medical Center
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Allentown
country: United States
facility: Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
city: Vancouver
country: United States
facility: Southwest Washington Medical Center Cancer Center
state: Washington
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: St. Mary's Hospital Medical Center - Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Manitowoc
country: United States
facility: Holy Family Memorial Medical Center Cancer Care Center
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology, Limited - Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology, Limited - Sturgeon Bay
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Marshfield Clinic - Wisconsin Rapids Center
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Debra Barton, RN, PhD, AOCN, FAAN
role: STUDY_CHAIR
References:
citation: Pruthi S, Qin R, Terstreip SA, Liu H, Loprinzi CL, Shah TR, Tucker KF, Dakhil SR, Bury MJ, Carolla RL, Steen PD, Vuky J, Barton DL. A phase III, randomized, placebo-controlled, double-blind trial of flaxseed for the treatment of hot flashes: North Central Cancer Treatment Group N08C7. Menopause. 2012 Jan;19(1):48-53. doi: 10.1097/gme.0b013e318223b021.
citation: Pruthi S, Qin R, Terstriep SA, et al.: The evaluation of flaxseed for hot flashes: results of a randomized, controlled trial, NCCTG study N08C7. [Abstract] J Clin Oncol 29 (Suppl 15): A-CRA9015, 2011.