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

NCT ID: NCT00295867

Last Updated: 2020-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-11-03
• Study Completion Date: 2013-12-31

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Zoledronic Acid

Patients women with early stage breast cancer and evidence of occult malignant cells in bone marrow aspirates following adjuvant chemotherapy will receive zoledronic acid (Zometa) 4mg, given intravenously over 15 minutes, once a month for two years.

Group Type: EXPERIMENTAL

Zoledronic Acid

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Zometa; Zoledronate

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hope S. Rugo, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Countries

United States

References

Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

Reference Type: DERIVED

PMID: 38979716 (View on PubMed)

Other Identifiers

UCSF-H6961-24352-02

Identifier Type: OTHER

Identifier Source: secondary_id

10-01674

Identifier Type: OTHER

Identifier Source: secondary_id

037519

Identifier Type: -

Identifier Source: org_study_id