Bone Mineral Density Effects of Zoledronate in Postmenopausal Women With Breast Cancer

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Completed
• CT.gov ID: NCT00213980
• Collaborator: (none)
• Enrollment: 68
• Location: 1
• Arms: 2
• Duration (Months): 99
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This is a two arm, double-blind randomized study looking at the effect of zoledronate, a bisphosphonate, on the bone mineral density (BMD) of postmenopausal women with breast cancer.

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

Detailed Description

This is a two arm, double-blind randomized study looking at the effect of zoledronate, a bisphosphonate, on the bone mineral density (BMD) of postmenopausal women with breast cancer. An approved bisphosphonate, alendronate, is of benefit in patients with osteoporosis, however, this agent has a roughly 30% incidence of gastrointestinal symptoms and up to 50% of patients may take the drug improperly, compromising absorption and potentially efficacy. Zoledronate is a heterocyclic imidazole third generation bisphosphonate, which is administered intravenously (IV) and has little toxicity. Zoledronate is more potent than alendronate, and because of its route of administration it does not have the problems of poor oral bioavailability and non-compliance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Bone Mineral Density Effects of Zoledronate in Postmenopausal Women With Breast Cancer
• Study Start Date: Jan 1, 2000
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Observation Observation only for 12 months
Active Comparator: Zoledronate Zoledronate	Drug: Zoledronate; 4 mg IV over 15 minutes administered once every 12 weeks times 4; Other Names: Zometa

Outcome Measures

Primary Outcome Measures

1. Change in Bone Mineral Density (BMD) From Baseline to 1 Year [Up to 1 year]

   To determine whether zoledronate 4 mg IV every 12 weeks x 4 doses is associated with increases in bone mineral density at the lumbar spine and femoral head, calculated from baseline and 1 year data. Participants who missed one or more DXA were not evaluated.

Secondary Outcome Measures

1. Rates of Metastases [Up to 1 year]

   Determine whether zoledronate is associated in rates of bone, visceral, and all distant metastases.

2. Overall Survival [Up to 10 years]

   Number of participants who survived from the start of treatment through off treatment, up to 10 years.

3. Clinical Toxicity of ZA [Up to 1 year]

   Tolerability and side effects of ZA, measured by the number of participants experiencing adverse events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Postmenopausal women, Stage III or axillary node positive

• Currently disease free of breast cancer and other invasive malignancies at the time of registration

• No concurrent use of bisphosphonates

Exclusion Criteria:

• Metastatic disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison

Investigators

• Principal Investigator: Daniel Mulkerin, MD, University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Wisconsin Carbone Cancer Center

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT00213980
• Other Study ID Numbers: CO99103; A534260; SMPH/MEDICINE/MEDICINE*H
• First Posted: Sep 21, 2005
• Last Update Posted: Nov 27, 2019
• Last Verified: Dec 1, 2017

• Keywords provided by University of Wisconsin, Madison: bone mineral density; postmenopausal women
• Additional relevant MeSH terms: Breast Neoplasms; Zoledronic Acid

Study Results

Participant Flow

Recruitment Details	The University of Wisconsin Comprehensive Cancer Center (UWCCC) conducted a clinical trial of adjuvant ZA in postmenopausal women with high-risk breast cancer, open through the Wisconsin Oncology Network (WON). Participants were recruited from 2000 through 2007.

Arm/Group Title	Observation	Zoledronic Acid (ZA)
Arm/Group Description	Observation only for 12 months	ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles
Period Title: Overall Study
STARTED	32	36
COMPLETED	26	29
NOT COMPLETED	6	7

Baseline Characteristics

Arm/Group Title	Observation	Zoledronic Acid (ZA)	Total
Arm/Group Description	Observation only for 12 months	ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles	Total of all reporting groups
Overall Participants	32	36	68
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	50.5	54.5	52.5
Sex: Female, Male (Count of Participants)
Female	32 100%	36 100%	68 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 2.8%	1 1.5%
Not Hispanic or Latino	32 100%	35 97.2%	67 98.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	32 100%	36 100%	68 100%
Tumor Size (Count of Participants)
=< 2cm	2 6.3%	14 38.9%	16 23.5%
2.1cm - 5cm	18 56.3%	11 30.6%	29 42.6%
> 5cm	9 28.1%	9 25%	18 26.5%
Inflammatory	3 9.4%	1 2.8%	4 5.9%
Unknown	0 0%	1 2.8%	1 1.5%
Lymph Node Status (Count of Participants)
Node negative	1 3.1%	1 2.8%	2 2.9%
Node positive	31 96.9%	35 97.2%	66 97.1%
Endocrine Therapy During Year 1 on Study (Count of Participants)
None	3 9.4%	5 13.9%	8 11.8%
Tamoxifen or other SERM	18 56.3%	23 63.9%	41 60.3%
Aromatase Inhibitor (AI)	5 15.6%	4 11.1%	9 13.2%
Tamoxifen switched to AI during study year	2 6.3%	1 2.8%	3 4.4%
No data available	4 12.5%	3 8.3%	7 10.3%
Performance Status (Count of Participants)
0	28 87.5%	31 86.1%	59 86.8%
1	3 9.4%	4 11.1%	7 10.3%
Unknown	1 3.1%	1 2.8%	2 2.9%

Outcome Measures

1. Primary Outcome

Title	Change in Bone Mineral Density (BMD) From Baseline to 1 Year
Description	To determine whether zoledronate 4 mg IV every 12 weeks x 4 doses is associated with increases in bone mineral density at the lumbar spine and femoral head, calculated from baseline and 1 year data. Participants who missed one or more DXA were not evaluated.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Fifty-six participants (ZA = 29, Observation = 27) were evaluable based on completing DXAs at 0, 6, and 12 months.

Arm/Group Title	Zoledronic Acid (ZA)	Observation
Arm/Group Description	ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles	Observation only for 12 months
Measure Participants	29	27
Lumbar Spine L1-L4 (L1-L4)	0.048	0.007
Femoral neck (FN)	0.014	0.005
Total femur (TF)	0.019	0.004
Trochanter (T)	0.023	0.005
Calcaneal (OC)	0.010	0.001

2. Secondary Outcome

Title	Rates of Metastases
Description	Determine whether zoledronate is associated in rates of bone, visceral, and all distant metastases.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected.

Arm/Group Title	Zoledronic Acid (ZA)	Observation
Arm/Group Description	ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles	Observation only for 12 months
Measure Participants	0	0

3. Secondary Outcome

Title	Overall Survival
Description	Number of participants who survived from the start of treatment through off treatment, up to 10 years.
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

Only participants who completed the trial (ZA = 29 and Observation = 26) were analyzed for this outcome measure.

Arm/Group Title	Zoledronic Acid (ZA)	Observation
Arm/Group Description	ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles	Observation only for 12 months
Measure Participants	29	26
Count of Participants [Participants]	24 75%	22 61.1%

4. Secondary Outcome

Title	Clinical Toxicity of ZA
Description	Tolerability and side effects of ZA, measured by the number of participants experiencing adverse events.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Data was collected for the ZA arm at 9 time points, and for the Observation arm at 2 time points.

Arm/Group Title	Zoledronic Acid (ZA)	Observation
Arm/Group Description	ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles	Observation only for 12 months
Measure Participants	36	32
Count of Participants [Participants]	36 112.5%	23 63.9%

Adverse Events

Time Frame	Adverse event data was collected for up to 48 weeks.
Adverse Event Reporting Description	Toxicity evaluation including telephone assessment occurred at 1 week after the start of each cycle. Toxicities for the Zoledronate arm were assessed at 9 time points, and toxicities for the Observation arm were assessed at 2 time points.
Arm/Group Title	Observation		Zoledronic Acid (ZA)
Arm/Group Description	Observation only for 12 months		ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles
All Cause Mortality
	Observation		Zoledronic Acid (ZA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Observation		Zoledronic Acid (ZA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Observation		Zoledronic Acid (ZA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/32 (71.9%)		36/36 (100%)
Cardiac disorders
Chest pain	0/32 (0%)		2/36 (5.6%)	2
Edema	2/32 (6.3%)	2	7/36 (19.4%)	11
Endocrine disorders
Hot Flash	13/32 (40.6%)	15	20/36 (55.6%)	36
Eye disorders
Eye pain	0/32 (0%)		2/36 (5.6%)	2
Gastrointestinal disorders
Constipation	0/32 (0%)		3/36 (8.3%)	3
Diarrhea	0/32 (0%)		2/36 (5.6%)	3
Nausea	0/32 (0%)		12/36 (33.3%)	15
General disorders
Arthralgia	3/32 (9.4%)	3	15/36 (41.7%)	30
Back pain	0/32 (0%)		2/36 (5.6%)	3
Bone pain	0/32 (0%)		5/36 (13.9%)	6
Fatigue	4/32 (12.5%)	4	27/36 (75%)	70
Fever	0/32 (0%)		4/36 (11.1%)	4
Headache	0/32 (0%)		20/36 (55.6%)	26
Pain	4/32 (12.5%)	5	4/36 (11.1%)	6
Rigors	0/32 (0%)		7/36 (19.4%)	9
Investigations
Weight Gain	0/32 (0%)		2/36 (5.6%)	2
Musculoskeletal and connective tissue disorders
Myalgia	5/32 (15.6%)	5	28/36 (77.8%)	54
Stiffness	0/32 (0%)		2/36 (5.6%)	2
Nervous system disorders
Lightheaded	0/32 (0%)		2/36 (5.6%)	3
Neuropathy-sensory	0/32 (0%)		5/36 (13.9%)	11
Vertigo	0/32 (0%)		4/36 (11.1%)	4
Respiratory, thoracic and mediastinal disorders
Cough	0/32 (0%)		2/36 (5.6%)	2
Skin and subcutaneous tissue disorders
Rash	0/32 (0%)		2/36 (5.6%)	3

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.