Risedronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy for Primary Breast Cancer - Full Text View

Sponsor:	North Central Cancer Treatment Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00054418

Purpose

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: This randomized phase III trial is studying two forms of calcium with or without risedronate to compare how well they work 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	Intervention	Phase
Breast Cancer Osteoporosis	Dietary Supplement: calcium carbonate Dietary Supplement: cholecalciferol Drug: risedronate sodium	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Double-Blind Primary Purpose: Supportive Care
Official Title:	A Phase III Randomized, Placebo-Controlled, Double-Blind Trial Of Risedronate (Actonel) For Prevention Of Bone Loss In Premenopausal Women Undergoing Chemotherapy For Primary Breast Carcinoma

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Calcium Cancer Osteoporosis

Drug Information available for: Cholecalciferol Risedronic acid Risedronate sodium Calcium gluconate Calcium carbonate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Average intra-patient change in lumbar spine (L2-L4, PA) bone mineral density (BMD) from baseline to one year after study entry

Secondary Outcome Measures:

Average intra-patient change in femoral neck and total hip BMD from baseline to one year after study entry
Incidence of osteopenia in the risedronate vs placebo groups at one year after study entry
Incidence of osteoporosis in the risedronate vs placebo groups at one year after study entry
Incidence of a 5% difference in intra-patient BMD scores at baseline
Serum and urine N-telopeptide and serum alkaline phosphatase at baseline and 6 months
Frequency and severity of toxicity as measured by NCI CTC version 2.0
Menopausal symptoms as measured by the Greene Climacteric Scale (GCS) at baseline, monthly during chemotherapy, at 6 months, 1 year, and 2 years after study entry
Association of baseline serum estradiol levels with permanent cessation of menses
Relationship between the subscales of the GCS (psychological, vasomotor, somatic and sexual) with type of chemotherapy, duration of chemotherapy, and menstrual cycle changes

Study Start Date:	March 2003
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Resectable 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 and no concurrent dental extraction, root canal, or dental implants
No prior bilateral oophorectomy

Other

No prior bisphosphonates
No other concurrent bisphosphonates

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00054418

Show 199 Study Locations

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Stephanie Hines, MD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Hines SL, Mincey BA, Sloan JA, Thomas SP, Chottiner E, Loprinzi CL, Carlson MD, Atherton PJ, Salim M, Perez EA. Phase III randomized, placebo-controlled, double-blind trial of risedronate for the prevention of bone loss in premenopausal women undergoing chemotherapy for primary breast cancer. J Clin Oncol. 2009 Mar 1;27(7):1047-53. Epub 2008 Dec 15.

ClinicalTrials.gov Identifier:	NCT00054418 History of Changes
Other Study ID Numbers:	CDR0000270449, NCCTG-N02C1
Study First Received:	February 5, 2003
Last Updated:	May 12, 2009
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

osteoporosis
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:

Breast Neoplasms
Osteoporosis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Calcium Carbonate
Cholecalciferol
Risedronic acid
Etidronic Acid

Antacids
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium Channel Blockers
Membrane Transport Modulators
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012