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

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT00295867
• Collaborator: Novartis (Industry)
• Enrollment: 45
• Location: 1
• Arm: 1
• Actual Duration (Months): 108.9
• Patients Per Site Per Month: 0.4

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Zoledronic Acid	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: Nov 3, 2004
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

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; Other Names: Zometa Zoledronate

Outcome Measures

Primary Outcome Measures

1. Response of Bone Marrow Micrometastases [up to 2 years]

   Median change in disseminated tumor cells (DTCs)/mL from baseline after 24 months

Secondary Outcome Measures

1. 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

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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

1. 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.

1. If the patient is to receive adjuvant chemotherapy, the aspiration will be performed at least three weeks after chemotherapy has been completed.

1. Adequate renal function as defined by:

1. Creatinine must be < upper limit of normal

1. Normal liver function tests including total bilirubin, alkaline phosphatase, and aspartate aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT)

2. Ability to understand and sign informed consent.

3. Concomitant hormonal therapy is allowed

4. Concomitant radiation therapy is allowed

5. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94115-1710

Sponsors and Collaborators

• University of California, San Francisco
• Novartis

Investigators

• Principal Investigator: Hope S. Rugo, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00295867
• Other Study ID Numbers: 037519; UCSF-H6961-24352-02; 10-01674
• First Posted: Feb 24, 2006
• Last Update Posted: May 12, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by University of California, San Francisco: stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Zoledronic Acid

Study Results

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.

Arm/Group Title	Zoledronic Acid
Arm/Group Description	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.
Period Title: Overall Study
STARTED	45
COMPLETED	34
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Zoledronic Acid
Arm/Group Description	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.
Overall Participants	45
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	45 100%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	46
Sex: Female, Male (Count of Participants)
Female	45 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	45 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Only 34 patients had bone marrow aspiration (BMA) at 24 mos required for this analysis

Arm/Group Title	Zoledronic Acid
Arm/Group Description	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.
Measure Participants	34
Median (Full Range) [DTCs/mL]	-4.5

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

N-telopeptide levels in urine data not collected

Arm/Group Title	Zoledronic Acid
Arm/Group Description	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.
Measure Participants	0

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zoledronic Acid
Arm/Group Description	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.
Measure Participants	34
Number [participants]	6 13.3%

Adverse Events

Time Frame	Two years
Arm/Group Title	Zoledronic Acid
Arm/Group Description	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.
All Cause Mortality
	Zoledronic Acid
	Affected / at Risk (%)	# Events
Total	2/45 (4.4%)
Serious Adverse Events
	Zoledronic Acid
	Affected / at Risk (%)	# Events
Total	1/45 (2.2%)
Gastrointestinal disorders
appendicitis	1/45 (2.2%)
Other (Not Including Serious) Adverse Events
	Zoledronic Acid
	Affected / at Risk (%)	# Events
Total	33/45 (73.3%)
Gastrointestinal disorders
grinding teeth	1/45 (2.2%)
Nausea	3/45 (6.7%)
Vomiting	2/45 (4.4%)
General disorders
Fatigue	14/45 (31.1%)
Fever	5/45 (11.1%)
Flu like symptoms	10/45 (22.2%)
Injury, poisoning and procedural complications
Soreness at infusion site	1/45 (2.2%)
Investigations
Creatinine increased	1/45 (2.2%)
Musculoskeletal and connective tissue disorders
Myalgia	18/45 (40%)
Back pain	2/45 (4.4%)
Bone pain	4/45 (8.9%)
Hip pain	1/45 (2.2%)
Jaw pain	1/45 (2.2%)
Arthralgia	2/45 (4.4%)
Nervous system disorders
Headache	1/45 (2.2%)
Lightheadedness	2/45 (4.4%)
Respiratory, thoracic and mediastinal disorders
Cough	1/45 (2.2%)
Skin and subcutaneous tissue disorders
Rash	1/45 (2.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.