Breast Cancer
Conditions
Keywords
bone mineral density, postmenopausal women
Brief summary
This is a two arm, double-blind randomized study looking at the effect of zoledronate, a bisphosphonate, on the bone mineral density (BMD) of postmenopausal women with breast cancer.
Detailed description
This is a two arm, double-blind randomized study looking at the effect of zoledronate, a bisphosphonate, on the bone mineral density (BMD) of postmenopausal women with breast cancer. An approved bisphosphonate, alendronate, is of benefit in patients with osteoporosis, however, this agent has a roughly 30% incidence of gastrointestinal symptoms and up to 50% of patients may take the drug improperly, compromising absorption and potentially efficacy. Zoledronate is a heterocyclic imidazole third generation bisphosphonate, which is administered intravenously (IV) and has little toxicity. Zoledronate is more potent than alendronate, and because of its route of administration it does not have the problems of poor oral bioavailability and non-compliance.
Interventions
DRUGZoledronate
4 mg IV over 15 minutes administered once every 12 weeks times 4
Sponsors
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Postmenopausal women, Stage III or axillary node positive * Currently disease free of breast cancer and other invasive malignancies at the time of registration * No concurrent use of bisphosphonates
Exclusion criteria
* Metastatic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bone Mineral Density (BMD) From Baseline to 1 Year | Up to 1 year | To determine whether zoledronate 4 mg IV every 12 weeks x 4 doses is associated with increases in bone mineral density at the lumbar spine and femoral head, calculated from baseline and 1 year data. Participants who missed one or more DXA were not evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Metastases | Up to 1 year | Determine whether zoledronate is associated in rates of bone, visceral, and all distant metastases. |
| Overall Survival | Up to 10 years | Number of participants who survived from the start of treatment through off treatment, up to 10 years. |
| Clinical Toxicity of ZA | Up to 1 year | Tolerability and side effects of ZA, measured by the number of participants experiencing adverse events. |
Countries
United States
Participant flow
Recruitment details
The University of Wisconsin Comprehensive Cancer Center (UWCCC) conducted a clinical trial of adjuvant ZA in postmenopausal women with high-risk breast cancer, open through the Wisconsin Oncology Network (WON). Participants were recruited from 2000 through 2007.
Participants by arm
| Arm | Count |
|---|---|
| Observation Observation only for 12 months | 32 |
| Zoledronic Acid (ZA) ZA
Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles | 36 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Developed ovarian cancer | 1 | 0 |
| Overall Study | Disease progression | 0 | 2 |
| Overall Study | Failed to obtain all 3 DXAs | 1 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Observation | Zoledronic Acid (ZA) | Total |
|---|---|---|---|
| Age, Continuous | 50.5 years | 54.5 years | 52.5 years |
| Endocrine Therapy During Year 1 on Study Aromatase Inhibitor (AI) | 5 Participants | 4 Participants | 9 Participants |
| Endocrine Therapy During Year 1 on Study No data available | 4 Participants | 3 Participants | 7 Participants |
| Endocrine Therapy During Year 1 on Study None | 3 Participants | 5 Participants | 8 Participants |
| Endocrine Therapy During Year 1 on Study Tamoxifen or other SERM | 18 Participants | 23 Participants | 41 Participants |
| Endocrine Therapy During Year 1 on Study Tamoxifen switched to AI during study year | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 35 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Lymph Node Status Node negative | 1 Participants | 1 Participants | 2 Participants |
| Lymph Node Status Node positive | 31 Participants | 35 Participants | 66 Participants |
| Performance Status 0 | 28 Participants | 31 Participants | 59 Participants |
| Performance Status 1 | 3 Participants | 4 Participants | 7 Participants |
| Performance Status Unknown | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 32 Participants | 36 Participants | 68 Participants |
| Sex: Female, Male Female | 32 Participants | 36 Participants | 68 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Tumor Size 2.1cm - 5cm | 18 Participants | 11 Participants | 29 Participants |
| Tumor Size =< 2cm | 2 Participants | 14 Participants | 16 Participants |
| Tumor Size > 5cm | 9 Participants | 9 Participants | 18 Participants |
| Tumor Size Inflammatory | 3 Participants | 1 Participants | 4 Participants |
| Tumor Size Unknown | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 32 | 36 / 36 |
| serious Total, serious adverse events | 0 / 32 | 0 / 36 |
Outcome results
Primary
Change in Bone Mineral Density (BMD) From Baseline to 1 Year
To determine whether zoledronate 4 mg IV every 12 weeks x 4 doses is associated with increases in bone mineral density at the lumbar spine and femoral head, calculated from baseline and 1 year data. Participants who missed one or more DXA were not evaluated.
Time frame: Up to 1 year
Population: Fifty-six participants (ZA = 29, Observation = 27) were evaluable based on completing DXAs at 0, 6, and 12 months.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Zoledronic Acid (ZA) | Change in Bone Mineral Density (BMD) From Baseline to 1 Year | Femoral neck (FN) | 0.014 grams per cubic centimeter |
| Zoledronic Acid (ZA) | Change in Bone Mineral Density (BMD) From Baseline to 1 Year | Trochanter (T) | 0.023 grams per cubic centimeter |
| Zoledronic Acid (ZA) | Change in Bone Mineral Density (BMD) From Baseline to 1 Year | Total femur (TF) | 0.019 grams per cubic centimeter |
| Zoledronic Acid (ZA) | Change in Bone Mineral Density (BMD) From Baseline to 1 Year | Calcaneal (OC) | 0.010 grams per cubic centimeter |
| Zoledronic Acid (ZA) | Change in Bone Mineral Density (BMD) From Baseline to 1 Year | Lumbar Spine L1-L4 (L1-L4) | 0.048 grams per cubic centimeter |
| Observation | Change in Bone Mineral Density (BMD) From Baseline to 1 Year | Calcaneal (OC) | 0.001 grams per cubic centimeter |
| Observation | Change in Bone Mineral Density (BMD) From Baseline to 1 Year | Lumbar Spine L1-L4 (L1-L4) | 0.007 grams per cubic centimeter |
| Observation | Change in Bone Mineral Density (BMD) From Baseline to 1 Year | Femoral neck (FN) | 0.005 grams per cubic centimeter |
| Observation | Change in Bone Mineral Density (BMD) From Baseline to 1 Year | Total femur (TF) | 0.004 grams per cubic centimeter |
| Observation | Change in Bone Mineral Density (BMD) From Baseline to 1 Year | Trochanter (T) | 0.005 grams per cubic centimeter |
Secondary
Clinical Toxicity of ZA
Tolerability and side effects of ZA, measured by the number of participants experiencing adverse events.
Time frame: Up to 1 year
Population: Data was collected for the ZA arm at 9 time points, and for the Observation arm at 2 time points.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoledronic Acid (ZA) | Clinical Toxicity of ZA | 36 Participants |
| Observation | Clinical Toxicity of ZA | 23 Participants |
Secondary
Overall Survival
Number of participants who survived from the start of treatment through off treatment, up to 10 years.
Time frame: Up to 10 years
Population: Only participants who completed the trial (ZA = 29 and Observation = 26) were analyzed for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoledronic Acid (ZA) | Overall Survival | 24 Participants |
| Observation | Overall Survival | 22 Participants |
Secondary
Rates of Metastases
Determine whether zoledronate is associated in rates of bone, visceral, and all distant metastases.
Time frame: Up to 1 year
Population: Data for this outcome measure was not collected.