Trial Outcomes & Findings for Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid (NCT NCT01409811)

Last Updated: 2020-05-08

Results Overview

After the trial's premature closure, no data were collected for the primary endpoints; however, data on 14 of 30 secondary endpoints were obtained and are summarized below. Serum level (pg/mL) per biomarker was log-transformed. Change from baseline over time was evaluated using a generalized linear mixed model where follow-up time was represented by terms for the sequence of post-baseline samples or for (log)day on study. To recognize regression to the mean across repeated samples, a term for biomarker level at baseline, with or without interaction by time, was included when it improved the model's fit to the observed data. With 14 biomarkers sampled twice after baseline, there were 28 evaluations of change in biomarker level with exposure to study drug. Therefore, to control the False Discovery Rate (FDR), only evaluations that maintained the study's FDR at no more than 5 percent were accepted as true.

Recruitment status

TERMINATED

Study phase

Target enrollment

9 participants

Primary outcome timeframe

"48-72 hrs" and "Surgery (10-23 days)"

Results posted on

2020-05-08

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Zoledronic Acid) Patients receive a single dose of zoledronic acid 4 mg IV over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-23. Tissue and blood samples from the initial biopsy and definitive surgery are collected to measure changes in biomarkers of tumor growth and metastasis, immunologic function, and the expression of genes important to breast cancer progression and metastasis. zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies therapeutic conventional surgery: Undergo definitive lumpectomy or mastectomy
Overall Study STARTED	9
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Zoledronic Acid) Patients receive a single dose of zoledronic acid 4 mg IV over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-23. Tissue and blood samples from the initial biopsy and definitive surgery are collected to measure changes in biomarkers of tumor growth and metastasis, immunologic function, and the expression of genes important to breast cancer progression and metastasis. zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies therapeutic conventional surgery: Undergo definitive lumpectomy or mastectomy
Overall Study Insurance denial	1

Baseline Characteristics

Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Zoledronic Acid) n=9 Participants Patients receive a single dose of zoledronic acid 4 mg IV over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-23. Tissue and blood samples from the initial biopsy and definitive surgery are collected to measure changes in biomarkers of tumor growth and metastasis, immunologic function, and the expression of genes important to breast cancer progression and metastasis. zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies therapeutic conventional surgery: Undergo definitive lumpectomy or mastectomy
Age, Continuous	61 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	6 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants

PRIMARY outcome

Timeframe: "48-72 hrs" and "Surgery (10-23 days)"

Population: The analysis included data from all evaluable subjects.

Outcome measures

Outcome measures
Measure	Treatment (Zoledronic Acid) n=8 Participants Patients receive a single dose of zoledronic acid 4 mg IV over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-23. Tissue and blood samples from the initial biopsy and definitive surgery are collected to measure changes in biomarkers of tumor growth and metastasis, immunologic function, and the expression of genes important to breast cancer progression and metastasis. zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies therapeutic conventional surgery: Undergo definitive lumpectomy or mastectomy
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline MIG @ Surgery (Day 10-23)	0.62 (log)pg/mL Standard Error 0.14
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline MCP-1 @ Surgery (Day 10-23)	-0.02 (log)pg/mL Standard Error 0.08
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline IFN-alpha per (log)Day until Surgery (Day 10-23)	-0.026 (log)pg/mL Standard Error 0.000
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline MIP1A per (log)Day until Surgery (Day 10-23)	0.12 (log)pg/mL Standard Error 0.05
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline MIG @ 48-72 hrs	2.31 (log)pg/mL Standard Error 0.24
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline IP-10 @ 48-72 hrs	1.47 (log)pg/mL Standard Error 0.18
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline IP-10 @ Surgery (Day 10-23)	0.16 (log)pg/mL Standard Error 0.08
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline IL-12 @ 48-72 hrs	0.23 (log)pg/mL Standard Error 0.06
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline IL-12 @ Surgery (Day 10-23)	-0.01 (log)pg/mL Standard Error 0.05
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline Eotaxin @ 48-72 hrs	-0.23 (log)pg/mL Standard Error 0.06
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline Eotaxin @ Surgery (Day 10-23)	0.02 (log)pg/mL Standard Error 0.06
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline IL-2R @ 48-72 hrs	0.17 (log)pg/mL Standard Error 0.04
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline IL-2R @ Surgery (Day 10-23)	0.10 (log)pg/mL Standard Error 0.11
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline IFN-gamma @ 48-72 hrs	0.04 (log)pg/mL Standard Error 0.01
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline IFN-gamma @ Surgery (Day 10-23)	-0.01 (log)pg/mL Standard Error 0.02
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline MIP1B @ 48-72 hrs	0.37 (log)pg/mL Standard Error 0.17
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline MIP1B @ Surgery (Day 10-23)	0.28 (log)pg/mL Standard Error 0.25
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline EGF @ 48-72 hrs	-0.18 (log)pg/mL Standard Error 0.10
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline EGF @ Surgery (Day 10-23)	0.25 (log)pg/mL Standard Error 0.12
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline MCP-1 @ 48-72 hrs	0.15 (log)pg/mL Standard Error 0.08

Adverse Events

Treatment (Zoledronic Acid)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Treatment (Zoledronic Acid) n=9 participants at risk Patients receive a single dose of zoledronic acid 4 mg IV over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-23. Tissue and blood samples from the initial biopsy and definitive surgery are collected to measure changes in biomarkers of tumor growth and metastasis, immunologic function, and the expression of genes important to breast cancer progression and metastasis. zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies therapeutic conventional surgery: Undergo definitive lumpectomy or mastectomy
Cardiac disorders Left ventricular systolic dysfunction	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Pulmonary valve disease	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Sinus bradycardia	22.2% 2/9 • Number of events 2 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Tricuspid valve disease	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Diarrhea	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Nausea	22.2% 2/9 • Number of events 2 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Chills	22.2% 2/9 • Number of events 2 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Edema limbs	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fever	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Infusion site extravasation	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Pain	22.2% 2/9 • Number of events 2 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Eye infection	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Injury, poisoning and procedural complications Bruising	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Alanine aminotransferase increased	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Aspartate aminotransferase increased	22.2% 2/9 • Number of events 2 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Cholesterol high	33.3% 3/9 • Number of events 3 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Creatinine increased	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Platelet count decreased	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations White blood cell decreased	11.1% 1/9 • Number of events 2 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypernatremia	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypertriglyceridemia	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypoglycemia	22.2% 2/9 • Number of events 2 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Back pain	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Bone pain	22.2% 2/9 • Number of events 2 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Myalgia	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Dizziness	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Headache	22.2% 2/9 • Number of events 2 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Chronic kidney disease	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Reproductive system and breast disorders Breast pain	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Cough	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Pruritus	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hematoma	22.2% 2/9 • Number of events 2 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hypertension	44.4% 4/9 • Number of events 4 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hypotension	11.1% 1/9 • Number of events 1 • Adverse events collected over a period of 2 years and 3 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Additional Information

Carolyn Behrendt, Ph.D.

City of Hope

Phone: 626-218-1148

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place