Trial Outcomes & Findings for Zoledronate in Treating Osteopenia or Osteoporosis in Postmenopausal Women Receiving Letrozole for Stage I, Stage II, or Stage IIIA Primary Breast Cancer (NCT NCT00436917)

NCT ID: NCT00436917

Last Updated: 2019-09-11

Results Overview

Change: BMD values at twelve months post study entry minus BMD values at baseline, expressed as a percentage of the baseline value.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 60 participants
• Primary outcome timeframe: Baseline and 1 year
• Results posted on: 2019-09-11

Participant Flow

Sixty participants were recruited between June 2006 and July 2007 at 6 individual sites participating in the Mayo Clinic Cancer Research Consortium (MCCRC).

Participant milestones

Measure	Zoledronic Acid 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Overall Study STARTED	53
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	21

Reasons for withdrawal

Measure	Zoledronic Acid 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Overall Study Withdrawal by Subject	13
Overall Study Adverse Event	2
Overall Study Physician Decision	1
Overall Study Death	1
Overall Study Lost to Follow-up	1
Overall Study Treatment for polymyalgia rheumatic	1
Overall Study Increased creatinine	1
Overall Study Personal conflicts of patient	1

Baseline Characteristics

Zoledronate in Treating Osteopenia or Osteoporosis in Postmenopausal Women Receiving Letrozole for Stage I, Stage II, or Stage IIIA Primary Breast Cancer

Baseline characteristics by cohort

Measure	Zoledronic Acid n=53 Participants 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Age, Continuous	66.9 years STANDARD_DEVIATION 10.0 • n=5 Participants
Sex: Female, Male Female	53 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	51 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Prior tamoxifen Yes	24 participants n=5 Participants
Prior tamoxifen No	29 participants n=5 Participants
Duration of tamoxifen use Missing	29 participants n=5 Participants
Duration of tamoxifen use <=2 years	4 participants n=5 Participants
Duration of tamoxifen use >2 years	20 participants n=5 Participants
Time since tamoxifen ended Missing	29 participants n=5 Participants
Time since tamoxifen ended <1 year	20 participants n=5 Participants
Time since tamoxifen ended >=1 year	4 participants n=5 Participants
Prior chemotherapy Yes	20 participants n=5 Participants
Prior chemotherapy No	33 participants n=5 Participants
Previous fracture by history or X-ray Yes	7 participants n=5 Participants
Previous fracture by history or X-ray No	46 participants n=5 Participants
Bone Mineral Density Measurement in Lumbar Spine	0.86 g/cm2 STANDARD_DEVIATION 0.12 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 1 year

Population: The primary analysis is performed on data where participants had the same baseline and 1 year BMD Lumbar Spine measurement location (L1-L4, L2-L4 or 'other Lumbar Spine')

Change: BMD values at twelve months post study entry minus BMD values at baseline, expressed as a percentage of the baseline value.

Outcome measures

Measure	Zoledronic Acid n=30 Participants 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Average Intra-patient Change in Total Lumbar Spine (L1 to L4) Bone Mineral Density (BMD)	2.66 Percentage of the baseline value Interval 1.27 to 4.62

SECONDARY outcome

Timeframe: Baseline and 2 year

Population: Analysis was performed on data where participants had the same baseline and 2 year BMD Lumbar Spine measurement location (L1-L4, L2-L4 or 'other Lumbar Spine')

Change: BMD values at year 2 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value.

Outcome measures

Measure	Zoledronic Acid n=27 Participants 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Average Intra-patient Change in Total Lumbar Spine (L1 to L4) Bone Mineral Density (BMD) at Year 2 Post Study Entry	4.94 Percentage of the baseline value Interval 2.2 to 7.68

SECONDARY outcome

Timeframe: Baseline and 3 year

Population: Analysis was performed on data where participants had the same baseline and 3 year BMD Lumbar Spine measurement location (L1-L4, L2-L4 or 'other Lumbar Spine')

Change: BMD values at year 3 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value.

Outcome measures

Measure	Zoledronic Acid n=22 Participants 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Average Intra-patient Change in Total Lumbar Spine (L1 to L4) Bone Mineral Density (BMD) at Year 3 Post Study Entry	6.20 Percentage of the baseline value Interval 3.74 to 8.66

SECONDARY outcome

Timeframe: Baseline and 4 year

Population: Analysis was performed on data where participants had the same baseline and 4 year BMD Lumbar Spine measurement location (L1-L4, L2-L4 or 'other Lumbar Spine')

Change: BMD values at year 4 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value.

Outcome measures

Measure	Zoledronic Acid n=13 Participants 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Average Intra-patient Change in Total Lumbar Spine (L1 to L4) Bone Mineral Density (BMD) at Year 4 Post Study Entry	6.99 Percentage of the baseline value Interval 0.8 to 13.18

SECONDARY outcome

Timeframe: Baseline and 5 year

Population: Analysis was performed on data where participants had the same baseline and 5 year BMD Lumbar Spine measurement location (L1-L4, L2-L4 or 'other Lumbar Spine')

Change: BMD values at year 5 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value.

Outcome measures

Measure	Zoledronic Acid n=11 Participants 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Average Intra-patient Change in Total Lumbar Spine (L1 to L4) Bone Mineral Density (BMD) at Year 5 Post Study Entry	11.71 Percentage of the baseline value Interval 2.43 to 21.0

SECONDARY outcome

Timeframe: Baseline and 1 year

Population: Analysis was performed on data where participants had the same baseline and 1 year BMD Femoral Neck measurement location (Left femoral, right femoral)

Change: BMD values at year 1 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value.

Outcome measures

Measure	Zoledronic Acid n=32 Participants 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Average Intra-patient Change in Femoral Neck Bone Mineral Density (BMD) at Year 1 Post Study Entry	5.66 Percentage of the baseline value Interval 1.3 to 10.02

SECONDARY outcome

Timeframe: Baseline and 2 year

Population: Analysis was performed on data where participants had the same baseline and 2 year BMD Femoral Neck measurement location (Left femoral, right femoral)

Change: BMD values at year 2 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value.

Outcome measures

Measure	Zoledronic Acid n=29 Participants 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Average Intra-patient Change in Femoral Neck Bone Mineral Density (BMD) at Year 2 Post Study Entry	10.47 Percentage of the baseline value Interval 2.14 to 18.8

SECONDARY outcome

Timeframe: Baseline and 3 year

Population: Analysis was performed on data where participants had the same baseline and 3 year BMD Femoral Neck measurement location (Left femoral, right femoral)

Change: BMD values at year 3 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value.

Outcome measures

Measure	Zoledronic Acid n=28 Participants 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Average Intra-patient Change in Femoral Neck Bone Mineral Density (BMD) at Year 3 Post Study Entry	8.44 Percentage of the baseline value Interval 3.45 to 13.44

SECONDARY outcome

Timeframe: Baseline and 4 year

Population: Analysis was performed on data where participants had the same baseline and 4 year BMD Femoral Neck measurement location (Left femoral, right femoral)

Change: BMD values at year 4 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value.

Outcome measures

Measure	Zoledronic Acid n=14 Participants 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Average Intra-patient Change in Femoral Neck Bone Mineral Density (BMD) at Year 4 Post Study Entry	4.49 Percentage of the baseline value Interval -0.98 to 9.96

SECONDARY outcome

Timeframe: Baseline and 5 year

Population: Analysis was performed on data where participants had the same baseline and 5 year BMD Femoral Neck measurement location (Left femoral, right femoral)

Change: BMD values at year 5 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value.

Outcome measures

Measure	Zoledronic Acid n=14 Participants 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Average Intra-patient Change in Femoral Neck Bone Mineral Density (BMD) at Year 5 Post Study Entry	4.54 Percentage of the baseline value Interval -3.18 to 12.26

SECONDARY outcome

Timeframe: 5 years

Adverse events were assessed per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Grade 1=Mild, Grade 2=Moderate.

Outcome measures

Measure	Zoledronic Acid n=53 Participants 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 1 Arthralgia	7 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 2 Arthralgia	4 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 3 Arthralgia	1 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 1 Creatinine Increase	7 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 2 Creatinite increase	2 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 2 Desquamating Rash	1 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 2 Headache	1 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 2 Hot flashes	3 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 1 Nausea	2 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 3 Pain in extremity	1 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 1 Fever	2 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 1 Vomiting	1 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 1 Musculoskeletal disorder	1 Participants
Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications Grade 2 Urogenital disorder	1 Participants

SECONDARY outcome

Timeframe: Up to 5 years

Population: None of the participants had disease progression.

Time to disease progression was defined as the time from date of randomization to the documentation of disease progression.

Outcome measures

Outcome data not reported

Adverse Events

Zoledronic Acid

Serious events: 1 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Measure	Zoledronic Acid n=52 participants at risk 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	1.9% 1/52 • Number of events 1 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.

Other adverse events

Measure	Zoledronic Acid n=52 participants at risk 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Gastrointestinal disorders Nausea	11.5% 6/52 • Number of events 7 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Gastrointestinal disorders Vomiting	3.8% 2/52 • Number of events 2 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
General disorders Fatigue	1.9% 1/52 • Number of events 1 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
General disorders Fever	7.7% 4/52 • Number of events 4 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Investigations Creatinine increased	21.2% 11/52 • Number of events 31 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Investigations INR increased	1.9% 1/52 • Number of events 1 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Musculoskeletal and connective tissue disorders Arthralgia	75.0% 39/52 • Number of events 128 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	3.8% 2/52 • Number of events 2 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Musculoskeletal and connective tissue disorders Myalgia	1.9% 1/52 • Number of events 1 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Musculoskeletal and connective tissue disorders Pain in extremity	1.9% 1/52 • Number of events 1 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Nervous system disorders Headache	1.9% 1/52 • Number of events 1 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Psychiatric disorders Depression	1.9% 1/52 • Number of events 1 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Renal and urinary disorders Urogenital disorder	1.9% 1/52 • Number of events 1 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Skin and subcutaneous tissue disorders Rash desquamating	1.9% 1/52 • Number of events 1 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Vascular disorders Hot flashes	5.8% 3/52 • Number of events 3 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.
Vascular disorders Hypertension	1.9% 1/52 • Number of events 1 • Adverse event data were collected every 6 months on treatment up to 5 years. One participant was excluded from adverse event reporting due to the adverse event data was not available beyond the baseline time point. Adverse event data were collected every 6 months on treatment up to 5 years.

Additional Information

Stephanie L. Hines, M.D.

Mayo Clinic Jacksonville

Phone: 507-266-0800

Email: hines.stephanie@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place