Breast Carcinoma Metastatic in the BonePhase 2NCT03070002
Denosumab in Treating Patients With ER and/or PR Positive, HER2 Negative Metastatic Breast Cancer With Bone Metastases and Detectable Circulating Tumor Cells
A Phase 2 study testing Denosumab and Laboratory Biomarker Analysis in people with Breast Carcinoma Metastatic in the Bone and Circulating Tumor Cell Count, run by Northwestern University at 2 sites in United States.
Trial summary
The purpose of this study is to look at the amount of cancer cells in the blood of participants who are being treated with denosumab. The other purpose is to look at how long it takes for cancer to get worse when participants are being treated with denosumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Carcinoma Metastatic in the Bone, Circulating Tumor Cell Count, Estrogen Receptor Positive
- What is being tested?
- Denosumab and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 2 sitesUnited States
- Study dates
- 19 Oct 2017to 24 Apr 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed ER and/or PR positive, HER-2/neu negative metastatic breast cancer; they can be enrolled in any line of therapy without investigational agents and should have stable disease or a partial response (which can be determined clinically) on current systemic treatment; patients must also have pathologic OR radiographic evidence of bone metastases and >= 5 CTCs; (Note: the pathology report that is used by the physician to determine diagnosis, will be used to determine patient eligibility; ER and PR status should be available at the time of registration)
- Patients may have either measurable or non-measurable within 30 of days of registration; (lesions treated with radiation therapy must not be used as a target lesion); (Note: per Response Evaluation Criteria in Solid Tumors [RECIST] criteria version [v.] 1.1, measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension; non-measurable disease is defined as all other lesions, including small lesions [longest diameter < 10 mm or pathological lymph nodes with P10 to < 15 mm short axis] as well as truly non-measurable lesions; lesions considered truly nonmeasurable include: leptomeningeal disease, ascites, pleural or pericardial effusion, and inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal masses/abdominal organomegaly identified by physical exam that is not measurable by reproducible imaging techniques)
- Patients may be enrolled in any line of standard treatment (without investigational agents); the start date of current treatment should be at least two 2 weeks or more prior to registration; (Note: patients will continue to receive the planned active treatment with chemotherapy or endocrine therapy [standard of care] and initiate denosumab at the recommended dose for this protocol)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Leukocytes >= 3,000/mcL (without growth factor)
- Platelets >= 100,000/mcL (with or without transfusion)
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- Hemoglobin >= 8 (with or without transfusion)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase [SGOT] and serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times institutional upper limit of normal (for patients with liver metastasis up to =< 5 times of upper limit of normal [ULN] is allowed)
- Bilirubin =< 1.5 ULN (for patients with liver metastasis up to =< 5 times of ULN is allowed)
- Serum creatinine =< 1.5 ULN
- Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (creatinine clearance should be calculated per institutional standard)
- Patients must have a serum calcium of >= 2.0 mmol/L (8.0 mg/dL) or albumin-adjusted serum calcium =< 2.9 mmol/L (11.5 mg/dL) within 30 days of registration; (Note: if patients are undergoing treatment for hypocalcemia and the serum calcium value at screening is > 8.0 mg/dl, then the patient will be eligible for this study)
- Females of child-bearing potential (FOCBP) and males with his or her partner must agree to use two acceptable methods of effective contraception, at study entry, for the duration of study participation, and for 5 months following completion of therapy; subjects who are surgically sterile (e.g., history of bilateral tubal ligation, hysterectomy) or whose sexual partner is sterile (e.g., history of vasectomy) are not required to use additional contraceptive measures; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; likewise, if a male patient impregnates his female partner, he should inform the treating physician immediately; NOTE: a FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy
- Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
- FOCBP must have a negative serum OR urine pregnancy test =< 7 days prior to registration
- Ability to understand and willingness to sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent document prior to registration
- Willingness and ability of subject to comply to study requirements
Who cannot join
- Patients may not be receiving any other investigational agents; a 2 week washout period for investigational agents is required before registration
- Patients with clinically symptomatic brain metastases or who required treatment for brain metastases within 4 weeks of registration (stable sequelae acceptable if treatment has been completed; these lesions cannot be used as target lesions)
- Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to denosumab are not eligible (i.e. same class of drugs) (Note: prior bisphosphonates are allowed; patients could have received bisphosphonates or be bisphosphonate-naive; patients who were previously on bisphosphonates can be enrolled in the study, as long as they have a wash-out period of 2 weeks prior to registration)
- Patients who are on corticosteroids or immunosuppressant's are not eligible; a 2 week wash-out period for is required before registration
- Patients who have a known additional malignancy that is progressing or requires active treatment are not eligible; patients who have had a prior diagnosis of cancer and if it has been < 3 years since their last treatment are also not eligible; NOTE: exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
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- Hypertension (defined as 160/90 mmHg for 3 consecutive readings 2-5 mins apart) that is not controlled on medication
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Psychiatric illness/social situations that would limit compliance with study requirements
- Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
- Subject is pregnant or breast feeding, or planning to become pregnant within 5 months after the end of treatment
- Known human immunodeficiency virus (HIV)-positive patients who are on combination antiretroviral therapy; (this is because of the potential for pharmacokinetic interactions with denosumab)
- No known prior history or current evidence of osteonecrosis/osteomyelitis of the jaw
- No known prior history or current evidence of untreated local gum or oral infection
- No known/planned active dental or jaw condition which requires oral surgery, including tooth extraction
- No known non-healed dental/oral surgery, including tooth extraction
- Patients have planned invasive dental procedures during the course of the study
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Northwestern University
Chicago, Illinois, 60611
Northwestern University- Lake Forest Hospital
Lake Forest, Illinois, 60045
About this study
Official title: A Phase II, Open Label Study to Evaluate Denosumab in Patients With ER and/or PR-Positive, HER2-Negative Metastatic Breast Cancer (MBC) With Bone Metastases and Detectable Circulating Tumor Cells (CTCs)
The purpose of this study is to look at the amount of cancer cells in the blood of participants who are being treated with denosumab. The other purpose is to look at how long it takes for cancer to get worse when participants are being treated with denosumab. Circulating tumor cells (CTCs) in the blood of patients with metastatic breast cancer (MBC) have been associated with shorter survival than when CTCs are absent, especially in patients whose cancer has spread to their bones. In this study, we want it see if denosumab (the study drug) will decrease the number of CTCs measured in patients with MBC and cancer that has spread to their bones. We also plan to get blood from participants to study other research markers of interest.
Read the detailed description
PRIMARY OBJECTIVES:
- To 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 circulating tumor cells (CTCs) by measuring the fraction of patients with reduction in CTCs after 3 cycles of denosumab.
SECONDARY OBJECTIVES:
- To assess the effect of denosumab on CTCs enumeration considered as a continuous variable (percent change from baseline) in this population.
II. To evaluate median progression-free survival (m-PFS).
TERTIARY OBJECTIVES:
- CTC enumeration after enrichment. II. To assess the effect on CTC profiling and characterization of stem cell phenotype (CTC-EMT).
III. To evaluate the type of progressive disease (new site versus [vs.] progression of lesions in previous sites).
IV. To analyze the expression of RANKL.
OUTLINE:
Patients receive denosumab subcutaneously (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.
After completion of study treatment, patients are followed up every 12 weeks for up to 2 years.
- Conditions
- Breast Carcinoma Metastatic in the Bone, Circulating Tumor Cell Count, Estrogen Receptor Positive, HER2/Neu Negative, Progesterone Receptor Positive, Stage IV Breast Cancer
- Being tested
- Denosumab, Laboratory Biomarker Analysis
- Medical subject headings
- Neoplastic Cells, Circulating, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabBiological
Also called AMG 162, AMG-162, Prolia, Xgeva
Given SC
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (denosumab) | Experimental | 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. Receives: Biological: Denosumab; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fraction of Patients With Reduction in CTCs
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.
Measured: Up to 3 months
Secondary outcomes (2)
Percent Change in CTCs
Evaluate the effect of denosumab on CTCs enumeration by assessing the percent change from baseline.
Measured: Baseline up to 3 months
Median Progression Free Survival
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.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2017
- Study start19 Oct 2017
- Primary completion6 Mar 2018
- Study completion24 Apr 2018
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast Carcinoma Metastatic in the BoneStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Sarika Jain, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03070002
- Sponsor's protocol ID
- NU 16B09
- Other IDs
- STU00203216, NU 16B09, P30CA060553, NCI-2017-00015
- Status last verified
- Oct 2018
- First submitted
- 27 Feb 2017
- Last updated
- 20 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open Label Study to Evaluate Denosumab in Patients With ER and/or PR-Positive, HER2-Negative Metastatic Breast Cancer (MBC) With Bone Metastases and Detectable Circulating Tumor Cells (CTCs)
- ClinicalTrials.gov ID
- NCT03070002
- Acronym / sponsor ID
- NU 16B09
- Conditions
- Breast Carcinoma Metastatic in the Bone, Circulating Tumor Cell Count, Estrogen Receptor Positive, HER2/Neu Negative, Progesterone Receptor Positive, Stage IV Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Amgen, National Cancer Institute (NCI)
- Study start
- 19 Oct 2017 (actual)
- Primary completion
- 6 Mar 2018 (actual)
- Study completion
- 24 Apr 2018 (actual)
- First posted
- 3 Mar 2017 (actual)
- Results
- Posted 20 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to look at the amount of cancer cells in the blood of participants who are being treated with denosumab. The other purpose is to look at how long it takes for cancer to get worse when participants are being treated with denosumab. Circulating tumor cells (CTCs) in the blood of patients with metastatic breast cancer (MBC) have been associated with shorter survival than when CTCs are absent, especially in patients whose cancer has spread to their bones. In this study, we want it see if denosumab (the study drug) will decrease the number of CTCs measured in patients with MBC and cancer that has spread to their bones. We also plan to get blood from participants to study other research markers of interest.
Detailed description
PRIMARY OBJECTIVES:
- To 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 circulating tumor cells (CTCs) by measuring the fraction of patients with reduction in CTCs after 3 cycles of denosumab.
SECONDARY OBJECTIVES:
- To assess the effect of denosumab on CTCs enumeration considered as a continuous variable (percent change from baseline) in this population.
II. To evaluate median progression-free survival (m-PFS).
TERTIARY OBJECTIVES:
- CTC enumeration after enrichment. II. To assess the effect on CTC profiling and characterization of stem cell phenotype (CTC-EMT).
III. To evaluate the type of progressive disease (new site versus [vs.] progression of lesions in previous sites).
IV. To analyze the expression of RANKL.
OUTLINE:
Patients receive denosumab subcutaneously (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.
After completion of study treatment, patients are followed up every 12 weeks for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (denosumab) | Experimental | Biological: Denosumab, Other: Laboratory Biomarker AnalysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically or cytologically confirmed ER and/or PR positive, HER-2/neu negative metastatic breast cancer; they can be enrolled in any line of therapy without investigational agents and should have stable disease or a partial response (which can be determined clinically) on current systemic treatment; patients must also have pathologic OR radiographic evidence of bone metastases and >= 5 CTCs; (Note: the pathology report that is used by the physician to determine diagnosis, will be used to determine patient eligibility; ER and PR status should be available at the time of registration)
- Patients may have either measurable or non-measurable within 30 of days of registration; (lesions treated with radiation therapy must not be used as a target lesion); (Note: per Response Evaluation Criteria in Solid Tumors [RECIST] criteria version [v.] 1.1, measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension; non-measurable disease is defined as all other lesions, including small lesions [longest diameter < 10 mm or pathological lymph nodes with P10 to < 15 mm short axis] as well as truly non-measurable lesions; lesions considered truly nonmeasurable include: leptomeningeal disease, ascites, pleural or pericardial effusion, and inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal masses/abdominal organomegaly identified by physical exam that is not measurable by reproducible imaging techniques)
- Patients may be enrolled in any line of standard treatment (without investigational agents); the start date of current treatment should be at least two 2 weeks or more prior to registration; (Note: patients will continue to receive the planned active treatment with chemotherapy or endocrine therapy [standard of care] and initiate denosumab at the recommended dose for this protocol)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Leukocytes >= 3,000/mcL (without growth factor)
Key exclusion criteria (18 listed)
- Patients may not be receiving any other investigational agents; a 2 week washout period for investigational agents is required before registration
- Patients with clinically symptomatic brain metastases or who required treatment for brain metastases within 4 weeks of registration (stable sequelae acceptable if treatment has been completed; these lesions cannot be used as target lesions)
- Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to denosumab are not eligible (i.e. same class of drugs) (Note: prior bisphosphonates are allowed; patients could have received bisphosphonates or be bisphosphonate-naive; patients who were previously on bisphosphonates can be enrolled in the study, as long as they have a wash-out period of 2 weeks prior to registration)
- Patients who are on corticosteroids or immunosuppressant's are not eligible; a 2 week wash-out period for is required before registration
- Patients who have a known additional malignancy that is progressing or requires active treatment are not eligible; patients who have had a prior diagnosis of cancer and if it has been < 3 years since their last treatment are also not eligible; NOTE: exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: AMG 162, AMG-162, Prolia, XgevaGiven SC | Biological | Treatment (denosumab) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (denosumab) |
Primary outcome
Fraction of Patients With Reduction in CTCs
Time frame: Up to 3 months
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.
2 secondary outcomes
Percent Change in CTCs
Time frame: Baseline up to 3 months
Median Progression Free Survival
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sarika Jain, MD principal investigator
Northwestern University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Denosumab and Laboratory Biomarker Analysis in people with Breast Carcinoma Metastatic in the Bone and Circulating Tumor Cell Count, run by Northwestern University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fraction of Patients With Reduction in CTCs (time frame: Up to 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2018.