Trial Outcomes & Findings for Bone Mineral Density Effects of Zoledronate in Postmenopausal Women With Breast Cancer (NCT NCT00213980)

Last Updated: 2019-11-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

68 participants

Primary outcome timeframe

Up to 1 year

Results posted on

2019-11-27

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Observation Observation only for 12 months	Zoledronic Acid (ZA) ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles
Overall Study STARTED	32	36
Overall Study COMPLETED	26	29
Overall Study NOT COMPLETED	6	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Observation Observation only for 12 months	Zoledronic Acid (ZA) ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles
Overall Study Withdrawal by Subject	3	1
Overall Study Adverse Event	1	1
Overall Study Disease progression	0	2
Overall Study Developed ovarian cancer	1	0
Overall Study Failed to obtain all 3 DXAs	1	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Observation n=32 Participants Observation only for 12 months	Zoledronic Acid (ZA) n=36 Participants ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles	Total n=68 Participants Total of all reporting groups
Age, Continuous	50.5 years n=5 Participants	54.5 years n=7 Participants	52.5 years n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	36 Participants n=7 Participants	68 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants n=5 Participants	35 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	32 Participants n=5 Participants	36 Participants n=7 Participants	68 Participants n=5 Participants
Tumor Size =< 2cm	2 Participants n=5 Participants	14 Participants n=7 Participants	16 Participants n=5 Participants
Tumor Size 2.1cm - 5cm	18 Participants n=5 Participants	11 Participants n=7 Participants	29 Participants n=5 Participants
Tumor Size > 5cm	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Tumor Size Inflammatory	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Tumor Size Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Lymph Node Status Node negative	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Lymph Node Status Node positive	31 Participants n=5 Participants	35 Participants n=7 Participants	66 Participants n=5 Participants
Endocrine Therapy During Year 1 on Study None	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Endocrine Therapy During Year 1 on Study Tamoxifen or other SERM	18 Participants n=5 Participants	23 Participants n=7 Participants	41 Participants n=5 Participants
Endocrine Therapy During Year 1 on Study Aromatase Inhibitor (AI)	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Endocrine Therapy During Year 1 on Study Tamoxifen switched to AI during study year	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Endocrine Therapy During Year 1 on Study No data available	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Performance Status 0	28 Participants n=5 Participants	31 Participants n=7 Participants	59 Participants n=5 Participants
Performance Status 1	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Performance Status Unknown	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 1 year

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

Outcome measures

Outcome measures
Measure	Zoledronic Acid (ZA) n=29 Participants ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles	Observation n=27 Participants Observation only for 12 months
Change in Bone Mineral Density (BMD) From Baseline to 1 Year Lumbar Spine L1-L4 (L1-L4)	0.048 grams per cubic centimeter Interval 0.034 to 0.062	0.007 grams per cubic centimeter Interval -0.02 to 0.034
Change in Bone Mineral Density (BMD) From Baseline to 1 Year Femoral neck (FN)	0.014 grams per cubic centimeter Interval 0.002 to 0.027	0.005 grams per cubic centimeter Interval -0.012 to 0.023
Change in Bone Mineral Density (BMD) From Baseline to 1 Year Total femur (TF)	0.019 grams per cubic centimeter Interval 0.011 to 0.026	0.004 grams per cubic centimeter Interval -0.006 to 0.015
Change in Bone Mineral Density (BMD) From Baseline to 1 Year Trochanter (T)	0.023 grams per cubic centimeter Interval 0.013 to 0.34	0.005 grams per cubic centimeter Interval -0.007 to 0.017
Change in Bone Mineral Density (BMD) From Baseline to 1 Year Calcaneal (OC)	0.010 grams per cubic centimeter Interval 0.004 to 0.015	0.001 grams per cubic centimeter Interval -0.007 to 0.005

SECONDARY outcome

Timeframe: Up to 1 year

Population: Data for this outcome measure was not collected.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 10 years

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

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

Outcome measures

Outcome measures
Measure	Zoledronic Acid (ZA) n=29 Participants ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles	Observation n=26 Participants Observation only for 12 months
Overall Survival	24 Participants	22 Participants

SECONDARY outcome

Timeframe: Up to 1 year

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

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

Outcome measures

Outcome measures
Measure	Zoledronic Acid (ZA) n=36 Participants ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles	Observation n=32 Participants Observation only for 12 months
Clinical Toxicity of ZA	36 Participants	23 Participants

Adverse Events

Observation

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Zoledronic Acid (ZA)

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Daniel Mulkerin

University of Wisconsin Carbone Cancer Center

Phone: 608-265-8090

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Observation n=32 participants at risk Observation only for 12 months	Zoledronic Acid (ZA) n=36 participants at risk ZA Zoledronic acid (ZA): 4 mg IV over 15 minutes administered once every 12 weeks for 4 cycles
General disorders Arthralgia	9.4% 3/32 • Number of events 3 • Adverse event data was collected for up to 48 weeks. 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.	41.7% 15/36 • Number of events 30 • Adverse event data was collected for up to 48 weeks. 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.
General disorders Back pain	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	5.6% 2/36 • Number of events 3 • Adverse event data was collected for up to 48 weeks. 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.
General disorders Bone pain	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	13.9% 5/36 • Number of events 6 • Adverse event data was collected for up to 48 weeks. 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.
Cardiac disorders Chest pain	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	5.6% 2/36 • Number of events 2 • Adverse event data was collected for up to 48 weeks. 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.
Gastrointestinal disorders Constipation	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	8.3% 3/36 • Number of events 3 • Adverse event data was collected for up to 48 weeks. 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.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	5.6% 2/36 • Number of events 2 • Adverse event data was collected for up to 48 weeks. 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.
Gastrointestinal disorders Diarrhea	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	5.6% 2/36 • Number of events 3 • Adverse event data was collected for up to 48 weeks. 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.
Cardiac disorders Edema	6.2% 2/32 • Number of events 2 • Adverse event data was collected for up to 48 weeks. 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.	19.4% 7/36 • Number of events 11 • Adverse event data was collected for up to 48 weeks. 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.
Eye disorders Eye pain	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	5.6% 2/36 • Number of events 2 • Adverse event data was collected for up to 48 weeks. 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.
General disorders Fatigue	12.5% 4/32 • Number of events 4 • Adverse event data was collected for up to 48 weeks. 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.	75.0% 27/36 • Number of events 70 • Adverse event data was collected for up to 48 weeks. 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.
General disorders Fever	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	11.1% 4/36 • Number of events 4 • Adverse event data was collected for up to 48 weeks. 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.
General disorders Headache	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	55.6% 20/36 • Number of events 26 • Adverse event data was collected for up to 48 weeks. 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.
Endocrine disorders Hot Flash	40.6% 13/32 • Number of events 15 • Adverse event data was collected for up to 48 weeks. 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.	55.6% 20/36 • Number of events 36 • Adverse event data was collected for up to 48 weeks. 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.
Nervous system disorders Lightheaded	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	5.6% 2/36 • Number of events 3 • Adverse event data was collected for up to 48 weeks. 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.
Musculoskeletal and connective tissue disorders Myalgia	15.6% 5/32 • Number of events 5 • Adverse event data was collected for up to 48 weeks. 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.	77.8% 28/36 • Number of events 54 • Adverse event data was collected for up to 48 weeks. 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.
Gastrointestinal disorders Nausea	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	33.3% 12/36 • Number of events 15 • Adverse event data was collected for up to 48 weeks. 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.
Nervous system disorders Neuropathy-sensory	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	13.9% 5/36 • Number of events 11 • Adverse event data was collected for up to 48 weeks. 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.
General disorders Pain	12.5% 4/32 • Number of events 5 • Adverse event data was collected for up to 48 weeks. 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.	11.1% 4/36 • Number of events 6 • Adverse event data was collected for up to 48 weeks. 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.
Skin and subcutaneous tissue disorders Rash	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	5.6% 2/36 • Number of events 3 • Adverse event data was collected for up to 48 weeks. 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.
General disorders Rigors	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	19.4% 7/36 • Number of events 9 • Adverse event data was collected for up to 48 weeks. 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.
Musculoskeletal and connective tissue disorders Stiffness	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	5.6% 2/36 • Number of events 2 • Adverse event data was collected for up to 48 weeks. 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.
Nervous system disorders Vertigo	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	11.1% 4/36 • Number of events 4 • Adverse event data was collected for up to 48 weeks. 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.
Investigations Weight Gain	0.00% 0/32 • Adverse event data was collected for up to 48 weeks. 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.	5.6% 2/36 • Number of events 2 • Adverse event data was collected for up to 48 weeks. 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.