Risedronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy for Primary Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00054418
First received: February 5, 2003
Last updated: November 12, 2013
Last verified: October 2013
  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: vitamin D
Drug: risedronate sodium
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
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:


Further study details as provided by Alliance for Clinical Trials in Oncology:

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 [ Time Frame: 1 year post study entry ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Average intra-patient change in femoral neck and total hip BMD from baseline to one year after study entry [ Time Frame: 1 year post study entry ] [ Designated as safety issue: No ]
  • Incidence of osteopenia in the risedronate vs placebo groups at one year after study entry [ Time Frame: 1 year post study entry ] [ Designated as safety issue: No ]
  • Incidence of osteoporosis in the risedronate vs placebo groups at one year after study entry [ Time Frame: 1 year post study entry ] [ Designated as safety issue: No ]
  • Incidence of a 5% difference in intra-patient BMD scores at baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Serum and urine N-telopeptide and serum alkaline phosphatase at baseline and 6 months [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • Frequency and severity of toxicity as measured by NCI CTC version 2.0 [ Time Frame: Up to 1 year post study treatment ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: Up to 2 years post study entry ] [ Designated as safety issue: No ]
  • Association of baseline serum estradiol levels with permanent cessation of menses [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Relationship between the subscales of the GCS (psychological, vasomotor, somatic and sexual) with type of chemotherapy, duration of chemotherapy, and menstrual cycle changes [ Time Frame: Up to 2 years post study entry ] [ Designated as safety issue: No ]

Enrollment: 216
Study Start Date: March 2003
Study Completion Date: May 2008
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: calcium carbonate, vitamin D and risedronate
Patients receive calcium carbonate 600 mg daily, vitamin D 400 U daily and risedronate 35 mg weekly.
Dietary Supplement: calcium carbonate
calcium 600 mg daily administered orally for one year
Dietary Supplement: vitamin D
vitamin D 400 U daily administered orally for one year
Drug: risedronate sodium
risedronate 35 mg weekly administered orally
Placebo Comparator: calcium carbonate, vitamin D and placebo
Patients receive calcium carbonate 600 mg daily, vitamin D 400 U daily and placebo weekly.
Dietary Supplement: calcium carbonate
calcium 600 mg daily administered orally for one year
Dietary Supplement: vitamin D
vitamin D 400 U daily administered orally for one year
Other: placebo
placebo tablet weekly administered orally for one year

Detailed Description:

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. In both arms, treatment begins during the first month of chemotherapy and continues for 1 year in the absence of unacceptable toxicity. For more information regarding the treatment arms, please see the "Arms" section below. 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. A summary of study goals is listed below.

Goals:

  1. To evaluate the effectiveness of risedronate at a weekly oral dose of 35 mg versus placebo in the prevention of bone loss in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.
  2. To evaluate the degree of bone loss over one year in premenopausal women undergoing adjuvant chemotherapy for primary breast cancer according to menopausal status at one year after therapy begins.
  3. To evaluate the relationship of current climacteric symptoms, menstrual and reproductive history, and chemotherapy regimen with ovarian failure (permanent cessation of menses) in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.
  4. To evaluate the relationship of baseline serum estradiol levels with ovarian failure in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  1. Required Characteristics

    1. Premenopausal women

      • ≤ 6 months since last menstrual period
      • no prior bilateral oophorectomy
      • not on estrogen replacement therapy
      • if TAH is performed, with at least one intact ovary, or if > 3 months since last menstrual period, then patients must have premenopausal estrogen levels ≤ 1 month of study entry
    2. Scheduled to undergo adjuvant or neoadjuvant chemotherapy for primary breast cancer (stages I-IIIB)
    3. ≥ 18 years of age
    4. ECOG performance status (PS) 0 or 1
  2. Contraindications

    1. Hypercalcemia (calcium level > 1mg/dL above UNL ≤ 6 months
    2. Hypocalcemia (calcium level > 0.5 mg/dL below UNL ≤ 6 months
    3. Inability to stand or sit upright for at least 30 minutes
    4. Known swallowing disorder
    5. Bone mineral density T score of ≤ - 2.0 at the hip or lumbar spine

      • a patient with a T score of - 2.1 is ineligible
      • a patient with a T score of - 1.9 is eligible
    6. History of vertebral compression fracture

      • Exception: traumatic fracture of the coccyx would not exclude a patient from participation
    7. Corticosteroids at doses > 5 mg daily of prednison or equivalent for > 2 weeks in the past 6 months
    8. Previous treatment with bisphosphonates
    9. Diseases affecting bone metabolism (hyperthyroidism, hyperparathyroidism, and hypercortisolism)
    10. History of severe renal impairment or creatinine > 2.0 mg/dL
    11. Malabsorption syndrome
    12. Estrogen replacement therapy
    13. Oral contraceptive use
    14. Prior bilateral oophorectomy
    15. Pregnant women

      • Nursing women
      • Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, injections, intrauterine device [IUD], surgical sterilization, abstinence, etc.)
      • This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
    16. Dental extraction, root canal, or implants ≤ 3 months prior to registration or planned during study treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 199 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Stephanie Hines, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00054418     History of Changes
Other Study ID Numbers: NCCTG-N02C1, NCI-2012-02515, CDR0000270449
Study First Received: February 5, 2003
Last Updated: November 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Trials in Oncology:
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
Risedronic acid
Calcium, Dietary
Vitamin D
Ergocalciferols
Etidronic Acid
Calcium Carbonate
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action
Micronutrients
Growth Substances
Calcium Channel Blockers
Membrane Transport Modulators
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2014