RATIONALE: Preventing bone loss in patients who are receiving chemotherapy for breast cancer may decrease the risk of fractures and may help patients live more comfortably. It is not yet known whether calcium is more effective with or without risedronate in preventing bone loss.

PURPOSE: Randomized phase III trial to compare the effectiveness of two forms of calcium with or without risedronate in preventing bone loss in premenopausal women who are receiving chemotherapy for primary stage I, stage II, stage IIIA, or stage IIIB breast cancer.

Condition	Treatment or Intervention	Phase
Osteoporosis stage I breast cancer stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer	Drug: calcium carbonate  Drug: cholecalciferol  Drug: risedronate  Procedure: complications of therapy assessment/management  Procedure: supportive care/therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the effectiveness of risedronate vs placebo in the prevention of bone loss in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.
• Compare the degree of bone loss over 1 year in these women according to menopausal status after 1 year of therapy.
• Determine the relationship of current climacteric symptoms, menstrual and reproductive history, and chemotherapy regimen with ovarian failure (permanent cessation of menses) in these women.
• Determine the relationship of baseline serum estradiol levels with ovarian failure in these women.

OUTLINE: This is a randomized, placebo-controlled, double-blind study. Patients are stratified according to planned tamoxifen therapy (yes vs no vs undecided), planned taxane therapy (yes vs no vs undecided), time from last menses (1-3 months vs longer than 3 months to 6 months), and age (under 40 vs 40 to 49 vs 50 and over). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral calcium and oral cholecalciferol daily and oral risedronate once weekly.
• Arm II: Patients receive calcium and cholecalciferol as in arm I and oral placebo once weekly. In both arms, treatment begins during the first month of chemotherapy and continues for 1 year in the absence of unacceptable toxicity.

Questionnaires about cessation of menses, ovarian failure, and menopausal symptoms are completed at baseline, monthly during chemotherapy, at 6 months, and then at 1 and 2 years.

Patients are followed for 1 year.

PROJECTED ACCRUAL: A total of 220 patients (110 per treatment arm) will be accrued for this study within 11 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Resected primary breast cancer
• Stage I-IIIB disease
• Scheduled to undergo adjuvant or neoadjuvant chemotherapy
• No hypercalcemia (calcium level greater than 1 mg/dL above upper limit of normal within the past 6 months)
• No hypocalcemia (calcium level greater than 0.5 mg/dL below lower limit of normal within the past 6 months)
• No diseases affecting bone metabolism (i.e., hyperparathyroidism, hyperthyroidism, and hypercortisolism)
• Bone mineral density T score of -2.0 or greater at the hip or spine (T score of -2.1 or less is ineligible)

PATIENT CHARACTERISTICS: Age

• 18 and over

Sex

• Female

Menopausal status

• Premenopausal meeting the following criteria:
• No more than 6 months since last menstrual period
• No prior bilateral oophorectomy
• Not on estrogen replacement therapy
• If total abdominal hysterectomy performed, then must have at least 1 intact ovary
• If more than 3 months since last menstrual period, then must have premenopausal estrogen levels within 1 month of study entry

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Creatinine no greater than 2.0 mg/dL
• No history of severe renal impairment

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• Able to stand or sit upright for at least 30 minutes
• No known swallowing disorder
• No history of vertebral compression fracture
• Traumatic fracture of the coccyx allowed
• No malabsorption syndrome

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• No concurrent estrogen
• No concurrent estrogen receptor modulators except tamoxifen
• No corticosteroid dose of prednisone or equivalent greater than 5 mg daily for more than 2 weeks within the past 6 months
• No concurrent estrogen replacement therapy
• No concurrent oral contraceptives

Radiotherapy

• Not specified

Surgery

• More than 3 months since prior dental extraction, root canal, or dental implants
• No prior bilateral oophorectomy

Other

• No prior bisphosphonates
• No other concurrent bisphosphonates

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36607,  United States; Recruiting
Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States; Recruiting
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States; Recruiting
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States; Recruiting
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States; Recruiting
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States; Recruiting
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States; Recruiting
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States; Recruiting
Michigan
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States; Recruiting
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States; Recruiting
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States; Recruiting
      Medcenter One Health System, Bismarck,  North Dakota,  58501-5505,  United States; Recruiting
Ohio
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States; Recruiting
Oklahoma
      CCOP - Oklahoma, Tulsa,  Oklahoma,  74136,  United States; Recruiting
Pennsylvania
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States; Recruiting
South Carolina
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States; Recruiting
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States; Recruiting
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States; Recruiting
Wisconsin
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States; Recruiting
Canada, Saskatchewan
      Allan Blair Cancer Centre at Pasqua Hospital, Regina,  Saskatchewan,  S4T 7T1,  Canada; Recruiting

Study chairs or principal investigators

Betty A. Mincey, MD,  Study Chair,  Mayo Clinic - Jacksonville   

Study ID Numbers:  CDR0000270449; NCCTG-N02C1; NCT00054418
Record last reviewed:  November 2004
Last Updated:  April 4, 2005
Record first received:  February 5, 2003
ClinicalTrials.gov Identifier:  NCT00054418
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08