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

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Osteoporosis; Breast Cancer

Treatments: Other: placebo; Drug: risedronate sodium; Dietary Supplement: calcium carbonate; Dietary Supplement: vitamin D

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00054418

NCCTG-N02C1

NCI-2012-02515 (Registry Identifier)

CDR0000270449 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 216 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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216 participants in 2 patient groups, including a placebo group

calcium carbonate, vitamin D and risedronate

Experimental group

Description:

Patients receive calcium carbonate 600 mg daily, vitamin D 400 U daily and risedronate 35 mg weekly.

Treatment:

Dietary Supplement: calcium carbonate

Dietary Supplement: vitamin D

Drug: risedronate sodium

calcium carbonate, vitamin D and placebo

Placebo Comparator group

Description:

Patients receive calcium carbonate 600 mg daily, vitamin D 400 U daily and placebo weekly.

Treatment:

Dietary Supplement: calcium carbonate

Dietary Supplement: vitamin D

Other: placebo