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

Primary Purpose

Breast Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Zoledronic Acid
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Breast Cancer focused on measuring stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria Women > 18 years of age with histologically or cytologically confirmed stage I, II or III breast cancer. If adjuvant chemotherapy is recommended, it must be completed before study start. 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. Adequate renal function as defined by: a. Creatinine must be < upper limit of normal Normal liver function tests including total bilirubin, alkaline phosphatase, and aspartate aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT) Ability to understand and sign informed consent. Concomitant hormonal therapy is allowed Concomitant radiation therapy is allowed Patients who have had surgery following neoadjuvant chemotherapy or hormonal therapy are eligible to participate in this trial Exclusion Criteria 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. 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. Karnofsky Performance status < 90%. Any significant medical condition that might interfere with treatment. Women participating in this study are not allowed to receive other bisphosphonate therapy during the study period, either oral or intravenous. Patients who are pregnant

Sites / Locations

  • University of California, San Francisco

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zoledronic Acid

Arm Description

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.

Outcomes

Primary Outcome Measures

Response of Bone Marrow Micrometastases
Median change in disseminated tumor cells (DTCs)/mL from baseline after 24 months

Secondary Outcome Measures

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
Number of Patients With Incidences of Distant Recurrence
Distant breast cancer recurrence is when the cancer has spread to another organ within the body.

Full Information

First Posted
February 23, 2006
Last Updated
May 4, 2020
Sponsor
University of California, San Francisco
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00295867
Brief Title
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

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
November 3, 2004 (Actual)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Novartis

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zoledronic Acid
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Zoledronic Acid
Other Intervention Name(s)
Zometa, Zoledronate
Intervention Description
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
Primary Outcome Measure Information:
Title
Response of Bone Marrow Micrometastases
Description
Median change in disseminated tumor cells (DTCs)/mL from baseline after 24 months
Time Frame
up to 2 years
Secondary Outcome Measure Information:
Title
Change in N-telopeptide Level
Description
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
Title
Number of Patients With Incidences of Distant Recurrence
Description
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Women > 18 years of age with histologically or cytologically confirmed stage I, II or III breast cancer. If adjuvant chemotherapy is recommended, it must be completed before study start. 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. Adequate renal function as defined by: a. Creatinine must be < upper limit of normal Normal liver function tests including total bilirubin, alkaline phosphatase, and aspartate aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT) Ability to understand and sign informed consent. Concomitant hormonal therapy is allowed Concomitant radiation therapy is allowed Patients who have had surgery following neoadjuvant chemotherapy or hormonal therapy are eligible to participate in this trial Exclusion Criteria 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. 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. Karnofsky Performance status < 90%. Any significant medical condition that might interfere with treatment. Women participating in this study are not allowed to receive other bisphosphonate therapy during the study period, either oral or intravenous. Patients who are pregnant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hope S. Rugo, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94115-1710
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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