Breast Cancer, Osteoporosis
Conditions
Keywords
osteoporosis, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer
Brief summary
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.
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.
Interventions
DIETARY_SUPPLEMENTcalcium carbonate
calcium 600 mg daily administered orally for one year
DIETARY_SUPPLEMENTvitamin D
vitamin D 400 U daily administered orally for one year
risedronate 35 mg weekly administered orally
OTHERplacebo
placebo tablet weekly administered orally for one year
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Average intra-patient change in lumbar spine (L2-L4, PA) bone mineral density (BMD) from baseline to one year after study entry | 1 year post study entry |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of osteopenia in the risedronate vs placebo groups at one year after study entry | 1 year post study entry |
| Incidence of osteoporosis in the risedronate vs placebo groups at one year after study entry | 1 year post study entry |
| Incidence of a 5% difference in intra-patient BMD scores at baseline | Baseline |
| Serum and urine N-telopeptide and serum alkaline phosphatase at baseline and 6 months | Up to 6 months |
| Average intra-patient change in femoral neck and total hip BMD from baseline to one year after study entry | 1 year post study entry |
| 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 | Up to 2 years post study entry |
| Association of baseline serum estradiol levels with permanent cessation of menses | Baseline |
| Relationship between the subscales of the GCS (psychological, vasomotor, somatic and sexual) with type of chemotherapy, duration of chemotherapy, and menstrual cycle changes | Up to 2 years post study entry |
| Frequency and severity of toxicity as measured by NCI CTC version 2.0 | Up to 1 year post study treatment |
Countries
Canada, United States
Outcome results
None listed