Trial Outcomes & Findings for Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms (NCT NCT01194440)

NCT ID: NCT01194440

Last Updated: 2018-09-12

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 63 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2018-09-12

Participant Flow

From February 2011 to January 2013, 59 women signed consent, met eligibility criteria, and received study intervention on this clinical trial at the Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins.

3 participants were screen failures and 1 participant withdrew consent prior to assignment to treatment.

Participant milestones

Measure	Arm I - IV Zoledronic Acid Prophylaxis Patients receive zoledronic acid IV at months 1 and 6. Beginning 14 days after first zoledronic acid infusion, patients receive oral letrozole once daily for 12 months in the absence of disease progression or unacceptable toxicity. letrozole: Given orally zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies enzyme-linked immunosorbent assay: Correlative studies mass spectrometry: Correlative studies bone scan: Correlative studies quality-of-life assessment: Ancillary studies questionnaire administration: Ancillary studies pharmacogenomic studies: Correlative studies high performance liquid chromatography: Correlative studies
Baseline (First Dose) STARTED	59
Baseline (First Dose) COMPLETED	52
Baseline (First Dose) NOT COMPLETED	7
6-months (2nd Dose) STARTED	52
6-months (2nd Dose) COMPLETED	48
6-months (2nd Dose) NOT COMPLETED	4

Reasons for withdrawal

Measure	Arm I - IV Zoledronic Acid Prophylaxis Patients receive zoledronic acid IV at months 1 and 6. Beginning 14 days after first zoledronic acid infusion, patients receive oral letrozole once daily for 12 months in the absence of disease progression or unacceptable toxicity. letrozole: Given orally zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies enzyme-linked immunosorbent assay: Correlative studies mass spectrometry: Correlative studies bone scan: Correlative studies quality-of-life assessment: Ancillary studies questionnaire administration: Ancillary studies pharmacogenomic studies: Correlative studies high performance liquid chromatography: Correlative studies
Baseline (First Dose) Reason not specified	4
Baseline (First Dose) Lack of Efficacy	1
Baseline (First Dose) Change in therapy	1
Baseline (First Dose) Adverse Event	1
6-months (2nd Dose) Change in therapy	4

Baseline Characteristics

Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms

Baseline characteristics by cohort

Measure	Arm I n=59 Participants Patients receive zoledronic acid IV at months 1 and 6. Beginning 14 days after first zoledronic acid infusion, patients receive oral letrozole once daily for 12 months in the absence of disease progression or unacceptable toxicity. letrozole: Given orally zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies enzyme-linked immunosorbent assay: Correlative studies mass spectrometry: Correlative studies bone scan: Correlative studies quality-of-life assessment: Ancillary studies questionnaire administration: Ancillary studies pharmacogenomic studies: Correlative studies high performance liquid chromatography: Correlative studies
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	46 Participants n=93 Participants
Age, Categorical >=65 years	13 Participants n=93 Participants
Sex: Female, Male Female	59 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Region of Enrollment United States	59 participants n=93 Participants

PRIMARY outcome

Timeframe: 12 months

Outcome measures

Measure

Arm I n=59 Participants Patients receive zoledronic acid IV at months 1 and 6. Beginning 14 days after first zoledronic acid infusion, patients receive oral letrozole once daily for 12 months in the absence of disease progression or unacceptable toxicity. letrozole: Given orally zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies enzyme-linked immunosorbent assay: Correlative studies mass spectrometry: Correlative studies bone scan: Correlative studies quality-of-life assessment: Ancillary studies questionnaire administration: Ancillary studies pharmacogenomic studies: Correlative studies high performance liquid chromatography: Correlative studies

Number of Participants With Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS)

22 Participants

SECONDARY outcome

Timeframe: Baseline, 1 month, 3 months, 6 months, 12 months

Population: Data was only collected in 58 participants at baseline, 52 participants at 1 month, 56 participants at 3 months, 51 participants at 6 months, and 45 participants at 12 months

The HAQ-DI score ranges from 0-3 with a higher score reflective of greater disability or increased incidence of AIMSS.

Outcome measures

Measure	Arm I n=58 Participants Patients receive zoledronic acid IV at months 1 and 6. Beginning 14 days after first zoledronic acid infusion, patients receive oral letrozole once daily for 12 months in the absence of disease progression or unacceptable toxicity. letrozole: Given orally zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies enzyme-linked immunosorbent assay: Correlative studies mass spectrometry: Correlative studies bone scan: Correlative studies quality-of-life assessment: Ancillary studies questionnaire administration: Ancillary studies pharmacogenomic studies: Correlative studies high performance liquid chromatography: Correlative studies
AIMSS as Determined by Health Assessment Questionnaire Disability Index (HAQ-DI) Score Baseline	0.2 score on a scale Interval 0.1 to 0.9
AIMSS as Determined by Health Assessment Questionnaire Disability Index (HAQ-DI) Score 1 month	0.2 score on a scale Interval 0.1 to 1.1
AIMSS as Determined by Health Assessment Questionnaire Disability Index (HAQ-DI) Score 3 months	0.1 score on a scale Interval 0.1 to 1.2
AIMSS as Determined by Health Assessment Questionnaire Disability Index (HAQ-DI) Score 6 months	0.2 score on a scale Interval 0.1 to 1.1
AIMSS as Determined by Health Assessment Questionnaire Disability Index (HAQ-DI) Score 12 months	0.4 score on a scale Interval 0.1 to 2.2

SECONDARY outcome

Timeframe: Baseline, 1 month, 3 months, 6 months, 12 months

Population: Data was only collected for 58 participants at baseline, 52 participants at 1 month, 55 participants at 3 months, 50 participants at 6 months, and 45 participants at 12 months

VAS is a visual measurement tool to assess AIMSS. It is a visual scale that ranges from 0 centimeters (cm) to 10cm. The VAS score ranges from zero (0cm) to 10 (10cm), with a higher score reflecting a greater frequency of AIMSS.

Outcome measures

Measure	Arm I n=58 Participants Patients receive zoledronic acid IV at months 1 and 6. Beginning 14 days after first zoledronic acid infusion, patients receive oral letrozole once daily for 12 months in the absence of disease progression or unacceptable toxicity. letrozole: Given orally zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies enzyme-linked immunosorbent assay: Correlative studies mass spectrometry: Correlative studies bone scan: Correlative studies quality-of-life assessment: Ancillary studies questionnaire administration: Ancillary studies pharmacogenomic studies: Correlative studies high performance liquid chromatography: Correlative studies
AIMSS as Determined by Visual Analog Scale (VAS) Score Baseline	0.8 score on a scale Interval 0.0 to 8.3
AIMSS as Determined by Visual Analog Scale (VAS) Score 1 month	1 score on a scale Interval 0.1 to 8.1
AIMSS as Determined by Visual Analog Scale (VAS) Score 3 months	1.4 score on a scale Interval 0.2 to 8.8
AIMSS as Determined by Visual Analog Scale (VAS) Score 6 months	1.2 score on a scale Interval 0.1 to 7.0
AIMSS as Determined by Visual Analog Scale (VAS) Score 12 months	1.9 score on a scale Interval 0.1 to 9.7

SECONDARY outcome

Timeframe: 12 months

Outcome measures

Measure

Arm I n=59 Participants Patients receive zoledronic acid IV at months 1 and 6. Beginning 14 days after first zoledronic acid infusion, patients receive oral letrozole once daily for 12 months in the absence of disease progression or unacceptable toxicity. letrozole: Given orally zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies enzyme-linked immunosorbent assay: Correlative studies mass spectrometry: Correlative studies bone scan: Correlative studies quality-of-life assessment: Ancillary studies questionnaire administration: Ancillary studies pharmacogenomic studies: Correlative studies high performance liquid chromatography: Correlative studies

Number of Participants Who Discontinue or Change Aromatase Inhibitor (AI) Therapy

5 Participants

Adverse Events

Arm I

Serious events: 0 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Arm I n=59 participants at risk Patients receive zoledronic acid IV at months 1 and 6. Beginning 14 days after first zoledronic acid infusion, patients receive oral letrozole once daily for 12 months in the absence of disease progression or unacceptable toxicity. letrozole: Given orally zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies enzyme-linked immunosorbent assay: Correlative studies mass spectrometry: Correlative studies bone scan: Correlative studies quality-of-life assessment: Ancillary studies questionnaire administration: Ancillary studies pharmacogenomic studies: Correlative studies high performance liquid chromatography: Correlative studies
Skin and subcutaneous tissue disorders Alopecia	8.5% 5/59 • Number of events 5 • Adverse events were collected throughout the 12 month intervention period.
Musculoskeletal and connective tissue disorders Arthralgia	42.4% 25/59 • Number of events 25 • Adverse events were collected throughout the 12 month intervention period.
Musculoskeletal and connective tissue disorders Arthritis	11.9% 7/59 • Number of events 7 • Adverse events were collected throughout the 12 month intervention period.
Musculoskeletal and connective tissue disorders Back Pain	5.1% 3/59 • Number of events 3 • Adverse events were collected throughout the 12 month intervention period.
Musculoskeletal and connective tissue disorders Bone Pain	6.8% 4/59 • Number of events 4 • Adverse events were collected throughout the 12 month intervention period.
General disorders Chills	8.5% 5/59 • Number of events 5 • Adverse events were collected throughout the 12 month intervention period.
Gastrointestinal disorders Constipation	8.5% 5/59 • Number of events 5 • Adverse events were collected throughout the 12 month intervention period.
Psychiatric disorders Depression	5.1% 3/59 • Number of events 3 • Adverse events were collected throughout the 12 month intervention period.
Gastrointestinal disorders Diarrhea	6.8% 4/59 • Number of events 4 • Adverse events were collected throughout the 12 month intervention period.
Nervous system disorders Dizziness	5.1% 3/59 • Number of events 3 • Adverse events were collected throughout the 12 month intervention period.
General disorders Edema Limbs	5.1% 3/59 • Number of events 3 • Adverse events were collected throughout the 12 month intervention period.
General disorders Fatigue	20.3% 12/59 • Number of events 12 • Adverse events were collected throughout the 12 month intervention period.
General disorders Fever	10.2% 6/59 • Number of events 6 • Adverse events were collected throughout the 12 month intervention period.
General disorders Flu-Like Symptoms	15.3% 9/59 • Number of events 9 • Adverse events were collected throughout the 12 month intervention period.
Vascular disorders Hot Flashes	61.0% 36/59 • Number of events 36 • Adverse events were collected throughout the 12 month intervention period.
Psychiatric disorders Insomnia	18.6% 11/59 • Number of events 11 • Adverse events were collected throughout the 12 month intervention period.
Musculoskeletal and connective tissue disorders Joint Range of Motion Decreased	18.6% 11/59 • Number of events 11 • Adverse events were collected throughout the 12 month intervention period.
Nervous system disorders Memory Impairment	5.1% 3/59 • Number of events 3 • Adverse events were collected throughout the 12 month intervention period.
Gastrointestinal disorders Nausea	11.9% 7/59 • Number of events 7 • Adverse events were collected throughout the 12 month intervention period.
Nervous system disorders Neuralgia	5.1% 3/59 • Number of events 3 • Adverse events were collected throughout the 12 month intervention period.
Musculoskeletal and connective tissue disorders Pain in Extremity	27.1% 16/59 • Number of events 16 • Adverse events were collected throughout the 12 month intervention period.
Nervous system disorders Peripheral Sensory Neuropathy	6.8% 4/59 • Number of events 4 • Adverse events were collected throughout the 12 month intervention period.
Reproductive system and breast disorders Vaginal Dryness	22.0% 13/59 • Number of events 13 • Adverse events were collected throughout the 12 month intervention period.

Additional Information

Dr. Vered Stearns

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phone: 443-287-6489

Email: HopkinsBreastTrials@jhmi.edu

Results disclosure agreements

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