Clinical trial NCT00295867: Zoledronate in Treating Bone Marrow Micrometastases in Women With Stage I, Stage II, or Stage III Breast Cancer
Official title: Pilot Study to Evaluate the Effect of Zoledronic Acid (Zometa) on Occult Malignant Bone Marrow Cells in Patients With High Risk Early Stage Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2006-02-24
Enrollment: 45
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Response of Bone Marrow Micrometastases
timeFrame: up to 2 years
Secondary outcomes:
measure: Change in N-telopeptide Level
timeFrame: up to 2 years
measure: Number of Patients With Incidences of Distant Recurrence
timeFrame: up to 5 years post initiation of treatment
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Hope S. Rugo, MD
role: PRINCIPAL_INVESTIGATOR
References: