Primary Hormone Receptor Negative Breast Cancer in Premenopausal Women
Conditions
Keywords
Breast Cancer, premenopausal, Bone Mineral density, Cancer therapy induced bone loss, zoledronic acid
Brief summary
Breast cancer and osteoporosis are two of the most frequent diseases in women. Estrogen may be associated with bone loss and the risk of breast cancer because of its potent effects on the mitotic activity of breast epithelium and on bone turnover. This study is will assess the safety and efficacy of Zoledronic acid 4 mg, given every 3 months over 24 months, in improving bone mineral density in premenopausal women with hormone receptor negative breast cancer and adjuvant chemotherapeutic treatment compared to placebo. This study is not recruiting patients in the United States.
Interventions
DRUGZoledronic Acid
4 mg zoledronic acid in 5 mL concentrate solution. Plastic vials.
DRUGPlacebo
Matching Placebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female patients with histologically confirmed incident invasive breast cancer (T1-4) with no evidence of regional lymph node metastasis (N0) or distant metastasis (M0) and after complete primary tumor resection and axillary lymph node dissection less than 90 days before start of study drug treatment. * Hormone receptor status is negative * Patient is premenopausal (spontaneous and regular menses with premenopausal estradiol levels (\>10ng/dL) * Patient receives adjuvant standard chemotherapy with approved cytotoxic chemotherapeutic drugs (e.g. AC 4-6 cycles) (prior neoadjuvant CT is allowed) * Bone density at study entry \> -2.5 T-Score
Exclusion criteria
* Prior treatment with bisphosphonates and estrogens or treatments for osteoporosis in addition to calcium and vitamin D * Severe physical or psychological concomitant diseases and other known concurrent, severe medical disorder jeopardizing the life of the patient in the immediate future (e.g., myocardial infarction in previous six months, angina pectoris despite treatment, uncontrolled severe arterial hypertension, progressive cardiac or respiratory failure) * Known hypersensitivity to bisphosphonates * Abnormal renal function * Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures and recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Bone Mineral Density (BMD) Measured by DXA at Lumbar Spine (L2-L4) Between Baseline and 24 Months. | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Development of Metastases as Assessed by X-ray, CT, or MRI During 24 Months and During 60 Months | 2 years |
| Bone Mineral Density (BMD) Measured by QUS at os Calcis and Phalanges After 24 Months | 2 years |
| Course of Biochemical Markers of Bone Turn Over (FSH, Estradiol (E2), Osteocalcin, PINP, Procollagene-I-peptid, Deoxypyridinoline in Serum) | 2 years |
| Pathologic Fractures During 24 Month | 2 years |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zoledronic Acid Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months. | 6 |
| Placebo Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months. | 5 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 1 |
Baseline characteristics
| Characteristic | Zoledronic Acid | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 41.2 Years STANDARD_DEVIATION 6.2 | 43.2 Years STANDARD_DEVIATION 2.6 | 42.1 Years STANDARD_DEVIATION 4.8 |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 6 / 6 |
| serious Total, serious adverse events | 1 / 5 | 1 / 6 |
Outcome results
Primary
Change in Bone Mineral Density (BMD) Measured by DXA at Lumbar Spine (L2-L4) Between Baseline and 24 Months.
Time frame: 24 months
Population: Analysis was not completed as study was not adequately powered due to premature study termination.
Secondary
Bone Mineral Density (BMD) Measured by QUS at os Calcis and Phalanges After 24 Months
Time frame: 2 years
Secondary
Course of Biochemical Markers of Bone Turn Over (FSH, Estradiol (E2), Osteocalcin, PINP, Procollagene-I-peptid, Deoxypyridinoline in Serum)
Time frame: 2 years
Secondary
Development of Metastases as Assessed by X-ray, CT, or MRI During 24 Months and During 60 Months
Time frame: 2 years
Secondary
Pathologic Fractures During 24 Month
Time frame: 2 years