Zoledronate in Treating Bone Marrow Micrometastases in Women With Stage I, Stage II, or Stage III Breast Cancer

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00295867
• Other study ID #: 037519
• Secondary ID: UCSF-H6961-24352
• Status: Completed
• Phase: Phase 2
• Start date: November 3, 2004
• Est. completion date: December 2013

Study information

• Verified date: May 2020
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 2013
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Zoledronic 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

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response of Bone Marrow Micrometastases	Median change in disseminated tumor cells (DTCs)/mL from baseline after 24 months	up to 2 years
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	up to 2 years
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.	up to 5 years post initiation of treatment