Breast Cancer
Conditions
Keywords
stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Brief summary
RATIONALE: Zoledronate may delay or prevent bone marrow metastases in patients with breast cancer. PURPOSE: This phase II trial is studying how well zoledronate works in treating bone marrow micrometastases in women with stage I, stage II, or stage III breast cancer.
Detailed description
OBJECTIVES: Primary * Determine the response of bone marrow micrometastases, as measured by immunocytochemistry/flow cytometry (IC/FC), during and after 2 years of treatment with zoledronate in women with stage I-III breast cancer. Secondary * Evaluate the effects of zoledronate on the bone osteoclast activation marker, n-telopeptide, in these patients. * Evaluate the incidence of distant recurrences in high-risk women with early-stage breast cancer and bone marrow micrometastases who receive adjuvant zoledronate. OUTLINE: This is a pilot study. Patients receive zoledronate IV over 15 minutes once a month for 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 months. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.
Interventions
DRUGZoledronic Acid
Zoledronic acid is a new, highly potent, heterocyclic nitrogen-containing third generation bisphosphonate that has demonstrated 40- to 850- fold greater potency than pamidronate in preclinical models of bone resorption. The mechanism of action of nitrogen-containing bisphosphonates such as pamidronate and zoledronic acid appears to involve inhibition of the mevalonate pathway
Sponsors
Novartis
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Women \> 18 years of age with histologically or cytologically confirmed stage I, II or III breast cancer. 2. If adjuvant chemotherapy is recommended, it must be completed before study start. 3. Bone marrow aspirate positive by IC/FC assay a. Definition of positive: \> 4 MM/ml b. Timing of bone marrow aspiration to determine study eligibility: i. If patient is to receive either no adjuvant therapy or hormonal therapy alone, the aspiration may be performed at diagnosis as part of the large MM study at University of California, San Francisco, or following diagnosis if the patient received initial surgery elsewhere. This is also true for patients who have surgery following neoadjuvant therapy for breast cancer. ii. If the patient is to receive adjuvant chemotherapy, the aspiration will be performed at least three weeks after chemotherapy has been completed. 4. Adequate renal function as defined by: a. Creatinine must be \< upper limit of normal 5. Normal liver function tests including total bilirubin, alkaline phosphatase, and aspartate aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT) 6. Ability to understand and sign informed consent. 7. Concomitant hormonal therapy is allowed 8. Concomitant radiation therapy is allowed 9. Patients who have had surgery following neoadjuvant chemotherapy or hormonal therapy are eligible to participate in this trial
Exclusion criteria
1. History of allergy to bisphosphonates. Acute phase reactions occur in up to 24% of patients and disappear with subsequent dosing. An acute phase reaction does not qualify as an allergic reaction. 2. History of renal insufficiency. Renal insufficiency is defined by a serum creatinine greater than the upper limit of normal or a creatinine clearance \< 50 mL/min due to any underlying cause. 3. Karnofsky Performance status \< 90%. 4. Any significant medical condition that might interfere with treatment. 5. Women participating in this study are not allowed to receive other bisphosphonate therapy during the study period, either oral or intravenous. 6. Patients who are pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response of Bone Marrow Micrometastases | up to 2 years | Median change in disseminated tumor cells (DTCs)/mL from baseline after 24 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in N-telopeptide Level | up to 2 years | N-telopeptide levels in urine will be recorded to evaluate the effect of zoledronic acid on bone mineralization (nmol bone collagen equivalents/mmol creatinine) at baseline and after 24 months on study treatment |
| Number of Patients With Incidences of Distant Recurrence | up to 5 years post initiation of treatment | Distant breast cancer recurrence is when the cancer has spread to another organ within the body. |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled between October 2004 and October 2007. Patients were recruited in a medical clinic at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| Zoledronic Acid Patients who had greater than 4 disseminated tumor cells (DTCs)/mL present following neoadjuvant or adjuvant chemotherapy for early stage breast cancer were treated with 4mg zoledronic acid each month for 24 months. | 45 |
| Total | 45 |
Baseline characteristics
| Characteristic | Zoledronic Acid |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants |
| Age, Continuous | 46 years |
| Region of Enrollment United States | 45 participants |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 45 |
| other Total, other adverse events | 33 / 45 |
| serious Total, serious adverse events | 1 / 45 |
Outcome results
Primary
Response of Bone Marrow Micrometastases
Median change in disseminated tumor cells (DTCs)/mL from baseline after 24 months
Time frame: up to 2 years
Population: Only 34 patients had bone marrow aspiration (BMA) at 24 mos required for this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zoledronic Acid | Response of Bone Marrow Micrometastases | -4.5 DTCs/mL |
Secondary
Change in N-telopeptide Level
N-telopeptide levels in urine will be recorded to evaluate the effect of zoledronic acid on bone mineralization (nmol bone collagen equivalents/mmol creatinine) at baseline and after 24 months on study treatment
Time frame: up to 2 years
Population: N-telopeptide levels in urine data not collected
Secondary
Number of Patients With Incidences of Distant Recurrence
Distant breast cancer recurrence is when the cancer has spread to another organ within the body.
Time frame: up to 5 years post initiation of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zoledronic Acid | Number of Patients With Incidences of Distant Recurrence | 6 participants |