Denosumab in Treating Patients With ER and/or PR Positive, HER2 Negative Metastatic Breast Cancer With Bone Metastases and Detectable Circulating Tumor Cells

• ClinicalTrials.gov Identifier: NCT03070002
• Recruitment Status: Terminated
• First Posted: March 3, 2017
• Results First Posted: November 20, 2018
• Last Update Posted: November 20, 2018
• Sponsor: Northwestern University
• Collaborators: Amgen; National Cancer Institute (NCI)
• Information provided by (Responsible Party): Northwestern University

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Breast Carcinoma Metastatic in the Bone; Circulating Tumor Cell Count; Estrogen Receptor Positive; HER2/Neu Negative; Progesterone Receptor Positive; Stage IV Breast Cancer
• Interventions: Biological: Denosumab; Other: Laboratory Biomarker Analysis
• Enrollment: 1

Participant Flow

Recruitment Details	The study opened for enrollment on March 23, 2017 with an accrual goal of 42 patients. The first patient started treatment on study October 19, 2017. The study closed permanently to enrollment on March 6 2018 with one patient enrolled, due to low accrual and before total accrual to the study could be met.
Pre-assignment Details

Arm/Group Title	Treatment (Denosumab)
Arm/Group Description	Patients receive denosumab SC on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression, unexpected toxicity, or patient withdrawal or death. Denosumab: Given SC Laboratory Biomarker Analysis: Correlative studies
Period Title: 3 Cycles of Treatment
Started	1
Completed	1
Not Completed	0
Period Title: Follow up for 2 Years
Started [1]	1
Completed	0
Not Completed	1
Reason Not Completed
Death	1
[1] Everyone that receives treatment on study goes into the follow up phase

Baseline Characteristics

Arm/Group Title		Treatment (Denosumab)
Arm/Group Description		Patients receive denosumab SC on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression, unexpected toxicity, or patient withdrawal or death. Denosumab: Given SC Laboratory Biomarker Analysis: Correlative studies
Overall Number of Baseline Participants		1
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	1 100.0%
	>=65 years	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	Female	1 100.0%
	Male	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	1 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	1 100.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	1 participants
		1 100.0%

Outcome Measures

1. Primary Outcome

Title	Fraction of Patients With Reduction in CTCs
Description	Assess the effect of denosumab in Her2/neu negative ER+ and/ or PR+ metastatic breast cancer patients who are in Partial Response (PR) or Stable Disease (SD) after starting systemic therapy with bone metastases and ≥ 5 CTCs by measuring the fraction of patients with reduction in CTCs.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

Data was not collected or analyzed for this outcome measure. The study was terminated early with only 1 patient enrolled.

Arm/Group Title	Treatment (Denosumab)
Arm/Group Description:	Patients receive denosumab SC on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression, unexpected toxicity, or patient withdrawal or death. Denosumab: Given SC Laboratory Biomarker Analysis: Correlative studies
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

2. Secondary Outcome

Title	Percent Change in CTCs
Description	Evaluate the effect of denosumab on CTCs enumeration by assessing the percent change from baseline.
Time Frame	Baseline up to 3 months

Outcome Measure Data

Analysis Population Description

Data was not collected or analyzed for this outcome measure. The study was terminated early with only 1 patient enrolled.

Arm/Group Title	Treatment (Denosumab)
Arm/Group Description:	Patients receive denosumab SC on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression, unexpected toxicity, or patient withdrawal or death. Denosumab: Given SC Laboratory Biomarker Analysis: Correlative studies
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

3. Secondary Outcome

Title	Median Progression Free Survival
Description	Assess median progression free survival (m-PFS) using statistical analysis evaluating the relationship between longitudinal CTC counts and PFS. PRS will be measured from the time of treatment up until progressive disease.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Data was not collected or analyzed for this outcome measure. The study was terminated early with only 1 patient enrolled.

Arm/Group Title	Treatment (Denosumab)
Arm/Group Description:	Patients receive denosumab SC on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression, unexpected toxicity, or patient withdrawal or death. Denosumab: Given SC Laboratory Biomarker Analysis: Correlative studies
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	Adverse events were collected for 3 cycles of treatment and up to 30 days past the last treatment, where 1 cycle of treatment equals 28 days.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Treatment (Denosumab)
Arm/Group Description	Patients receive denosumab SC on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression, unexpected toxicity, or patient withdrawal or death. Denosumab: Given SC Laboratory Biomarker Analysis: Correlative studies
All-Cause Mortality
	Treatment (Denosumab)
	Affected / at Risk (%)
Total	1/1 (100.00%)
Serious Adverse Events
	Treatment (Denosumab)
	Affected / at Risk (%)
Total	0/1 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Treatment (Denosumab)
	Affected / at Risk (%)
Total	1/1 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	1/1 (100.00%)
Gastrointestinal disorders
Nausea † 1	1/1 (100.00%)
Gastrointestinal pain † 1	1/1 (100.00%)
Abdominal pain † 1	1/1 (100.00%)
Investigations
Alanine aminotransferase increased † 1	1/1 (100.00%)
Aspartate aminotransferase increased † 1	1/1 (100.00%)
Alkaline phosphatase increased † 1	1/1 (100.00%)
Metabolism and nutrition disorders
Hypercalcemia † 1	1/1 (100.00%)
Hypokalemia † 1	1/1 (100.00%)
Hypoabuminemia † 1	1/1 (100.00%)
Musculoskeletal and connective tissue disorders
Bone pain † 1	1/1 (100.00%)
Back pain † 1	1/1 (100.00%)
Nervous system disorders
Dizziness † 1	1/1 (100.00%)
Respiratory, thoracic and mediastinal disorders
Hoarsness † 1	1/1 (100.00%)
1 Term from vocabulary, CTCAE (4.03); † Indicates events were collected by systematic assessment

Limitations and Caveats

The study was terminated early with only 1 patient enrolled due to slow accrual.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: MASSIMO CRISTOFANILLI, MD
• Organization: Northwestern University
• Phone: 312-503-1114
• EMail: massimo.cristofanilli@nm.org

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT03070002
• Other Study ID Numbers: NU 16B09; STU00203216 ( CTRP (Clinical Trial Reporting Program) ); NU 16B09 ( Other Identifier: Northwestern University ); P30CA060553 ( U.S. NIH Grant/Contract ); NCI-2017-00015 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
• First Submitted: February 27, 2017
• First Posted: March 3, 2017
• Results First Submitted: October 22, 2018
• Results First Posted: November 20, 2018
• Last Update Posted: November 20, 2018