Black Cohosh in Treating Hot Flashes in Women Who Have or Who Are At Risk of Developing Breast Cancer

A Phase III Double-Blind, Randomized, Placebo-Controlled Crossover Trial Of Black Cohosh In The Management Of Hot Flashes

RATIONALE: The herbal supplement black cohosh may be effective in relieving hot flashes in women.

PURPOSE: Randomized phase III trial to determine the effectiveness of black cohosh in relieving hot flashes in women who have breast cancer or who are at risk of developing breast cancer.

OBJECTIVES:

• Compare the efficacy of black cohosh vs placebo in diminishing hot flash activity in women with breast cancer OR a concern about taking hormones because of a fear of breast cancer.
• Determine whether continued use of this drug by these patients leads to prolonged reduction of the hot flash score with minimal toxic effects.
• Correlate the reduction of hot flash score with improvement in quality of life and related outcomes in patients treated with this drug.
• Determine the toxic effects of this drug in these patients.
• Determine whether abnormal sweating is decreased in patients treated with this drug.

OUTLINE: This is a randomized, double-blind, placebo-controlled, crossover study. Patients are stratified according to age (18 to 49 vs 50 and over), current tamoxifen use (yes vs no vs unknown), current raloxifene use (yes vs no vs unknown), current aromatase inhibitor use (yes vs no), duration of hot flash symptoms (less than 9 months vs 9 months or more), and average frequency of hot flashes per day (2-3 vs 4-9 vs 10 or more). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral black cohosh twice daily for 4 weeks.
• Arm II: Patients receive oral placebo twice daily for 4 weeks. All patients then cross over to the other arm and receive treatment as above for 4 weeks.

After completion of the crossover treatment, all patients may opt to receive open-label black cohosh for an additional 8 weeks.

Patients complete a hot flash diary daily at baseline and during the 8-week double-blind study, and then daily for 8 weeks during optional open-label treatment.

Patients who opt to receive open-label black cohosh are followed at 6 months, 1 year, and 2 years.

PROJECTED ACCRUAL: A total of 110 patients (55 patients per arm) will be accrued for this study within 6-11 months.

DISEASE CHARACTERISTICS:

• History of breast cancer OR concern about taking hormones because of fear of breast cancer

  • No current active disease
  • No current evidence of malignant disease

• Bothersome hot flashes

  • Patient-reported occurrence at least 14 times per week and of sufficient severity to make the patient desire therapeutic intervention

• Hormone receptor status:

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to complete questionnaires alone or with assistance

PRIOR CONCURRENT THERAPY:

Chemotherapy

• More than 4 weeks since prior antineoplastic chemotherapy
• No concurrent antineoplastic chemotherapy during the double-blind portion of the study

Endocrine therapy

• More than 4 weeks since prior androgens, estrogens, or progestational agents

• More than 2 weeks since prior dehydroepiandrosterone (DHEA) for hot flashes

• No concurrent androgens, estrogens, or progestational agents during the double-blind portion of the study

• No concurrent DHEA for hot flashes

• Concurrent tamoxifen, raloxifene, or an aromatase inhibitor is allowed provided the patient started the drug at least 4 weeks prior to study entry and plans to continue the drug throughout the double-blind portion of the study Other

• More than 2 weeks since prior antidepressants

• More than 2 weeks since other prior agents for treating hot flashes (e.g., clonidine or Bellergal-s)

• No prior black cohosh

• No concurrent antidepressants during the double-blind portion of the study

• No other concurrent agents for treating hot flashes (e.g., clonidine or Bellergal-s)

  • Concurrent vitamin E and/or soy allowed provided patient is on a stable dose for at least 1 month prior to study entry and plans to continue the same dose throughout study duration

• No concurrent oral herbal therapies or therapeutic herbal teas or tinctures except beverage teas (e.g., chamomile, ginger, peppermint, lemongrass, and fruit-based tea)