Breast CancerEarly Phase 1NCT02900469
Presurgical Trial of Denosumab in Breast Cancer
A Early Phase 1 study testing denosumab and Surgery in people with Breast Cancer, run by NYU Langone Health at 1 site in United States.
Trial summary
The purpose of this study is to determine whether one dose of denosumab can lead to changes in the tumor, which may decrease the ability of tumor to spread. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- denosumab and Surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2016to 3 Jan 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed invasive breast cancer (stages I-III) who have undergone core needle biopsy (clinically or radiographically at least T1c to allow adequate residual cancer tissue at surgery) and will be scheduled for surgical resection (i.e. segmental excision or mastectomy).
- Archival tissue freshly cut from core biopsy must be available; patients who had a diagnostic core biopsy at an outside institution are eligible as long as it is confirmed that tumor specimens in paraffin blocks (preferred) or ≥ 25 unstained slides, with an associated pathology report, are available.
- Female, Age ≥18 years (pre or postmenopausal).
- Signed informed consent
- Serum calcium or albumin-adjusted serum calcium ≥2.0mmol/L (8.0mg/dL) and ≤ 2.9 mmol/L (11.5mg/dL)
- Patients with reproductive potential must be willing to use, in combination with her partner, 2 acceptable methods of effective contraception or practice sexual abstinence throughout the study and continue for 5 months after study duration. Subjects who are surgically sterile (eg, history of bilateral tubal ligation, hysterectomy) or whose sexual partner is sterile (eg, history of vasectomy) are not required to use additional contraceptive measures.
Who cannot join
- Consideration for neoadjuvant therapy
- Serious infections including a history of active Hepatitis B, Hepatitis C or HIV
- Subject has known sensitivity to any of the products to be administered during the study (e.g.., mammalian derived products, calcium, or vitamin D)
- Subject is pregnant or breast feeding, or planning to become pregnant/breastfeed while on study through 5 months after the end of treatment
- Patients have prior history or current evidence of osteonecrosis or osteomyelitis of the jaw, evidence of untreated local gum or oral infection, or non-healed dental or oral surgery
- Patients with active dental or jaw conditions which require oral surgery/dental procedures, including tooth extraction for the course of the study
Trial locations and contacts
1 site in 1 country.
United States1 site
NYU Perlmutter Cancer Center
New York, New York, 10016
About this study
Official title: Pre-surgical Evaluation of Denosumab in Patients With Operable Invasive Breast Cancer
The purpose of this study is to determine whether one dose of denosumab can lead to changes in the tumor, which may decrease the ability of tumor to spread.
Read the detailed description
Breast cancer is the most common cancer among women, affecting one in eight women, and is the second leading cause of mortality from cancer. Bone metastases are a frequent complication of breast cancer, and the mechanism of breast cancer metastases to bone is an ongoing area of research.. Receptor activator of NF-kB (RANK) and its ligand (RANKL) have been identified and characterized for its role in bone remodeling. RANKL is a member of the tumor necrosis factor (TNF) family of cytokines that binds to its receptor RANK to control osteoclast differentiation, activation, and survival. RANK protein expression is not only found on osteoclasts and dendritic cells but also on T cells and mammary epithelial cells. RANK and RANKL is important for lymph node and thymus formation as well as lactating mammary gland development during pregnancy. Furthermore, the RANK/RANKL axis has been linked to progestin driven breast carcinomas and bone metastases.
RANK is expressed in 6-57% of invasive human breast cancers (depending upon the parameters for defining positivity and antibodies utilized for immunohistochemistry (IHC)), and RANKL driven hormone (progesterone -dependent proliferation, survival, and nonproliferative expansion of mammary stem cells may contribute to breast cancer initiation, progression, and recurrence.
We hypothesize that denosumab can inhibit RANKL signaling in early breast tumors which express RANK, inhibiting pro-metastatic mechanisms and reducing immunosuppression in the tumor microenvironment. This will be tested in a pre-surgical clinical trial (Phase 0) to evaluate and select the pharmacodynamics markers of RANKL inhibition in breast cancer.
- Conditions
- Breast Cancer
- Being tested
- denosumab, Surgery
- Keywords
- RANK, RANKL
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
denosumabBiological
Also called Xgeva
denosumab: 120 mg subcutaneous injection
SurgeryProcedure or surgery
Surgery: approximately 2-4 weeks after dosing of denosumab
| Study group | Role | What they receive |
|---|---|---|
| Denosumab & surgery | Experimental | denosumab: 120 mg subcutaneous injection
Surgery: 2-4 weeks after denosumab Receives: Biological: denosumab; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacodynamic markers of RANKL inhibition determination
Immunohistochemical analyses (IHC) of RANK and RANKL protein expression will be performed by Clarient Diagnostics Services Inc., Aliso Viejo, CA using prototype assays developed and optimized by Dako on their automated staining platform
Measured: Change from baseline RANKL inhibition determination at one month
Secondary outcomes (1)
Frequency of RANK and RANKL protein expression (by IHC) in operable breast cancer using Immunohistochemical analyses (IHC)
Immunohistochemical analyses (IHC) of RANK and RANKL protein expression will be performed by Clarient Diagnostics Services Inc., Aliso Viejo, CA using prototype assays developed and optimized by Dako on their automated staining platform
Measured: Change from baseline frequency of RANK and RANKL protein expression at one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2016 (estimated)
- Study startOct 2016
- Primary completion3 Dec 2019
- Study completion3 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sylvia Adams, MD, Principal investigator, NYU Perlmutter Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02900469
- Sponsor's protocol ID
- s14-01311
- Status last verified
- Aug 2020
- First submitted
- 29 Aug 2016
- Last updated
- 21 Aug 2020
- Results posted
- No
- 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 21 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-surgical Evaluation of Denosumab in Patients With Operable Invasive Breast Cancer
- ClinicalTrials.gov ID
- NCT02900469
- Acronym / sponsor ID
- s14-01311
- Conditions
- Breast Cancer
- Keywords
- RANK, RANKL
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Oct 2016
- Primary completion
- 3 Dec 2019 (actual)
- Study completion
- 3 Jan 2020 (actual)
- First posted
- 14 Sep 2016 (estimated)
- Results
- Not posted in the source record
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 determine whether one dose of denosumab can lead to changes in the tumor, which may decrease the ability of tumor to spread.
Detailed description
Breast cancer is the most common cancer among women, affecting one in eight women, and is the second leading cause of mortality from cancer. Bone metastases are a frequent complication of breast cancer, and the mechanism of breast cancer metastases to bone is an ongoing area of research.. Receptor activator of NF-kB (RANK) and its ligand (RANKL) have been identified and characterized for its role in bone remodeling. RANKL is a member of the tumor necrosis factor (TNF) family of cytokines that binds to its receptor RANK to control osteoclast differentiation, activation, and survival. RANK protein expression is not only found on osteoclasts and dendritic cells but also on T cells and mammary epithelial cells. RANK and RANKL is important for lymph node and thymus formation as well as lactating mammary gland development during pregnancy. Furthermore, the RANK/RANKL axis has been linked to progestin driven breast carcinomas and bone metastases.
RANK is expressed in 6-57% of invasive human breast cancers (depending upon the parameters for defining positivity and antibodies utilized for immunohistochemistry (IHC)), and RANKL driven hormone (progesterone -dependent proliferation, survival, and nonproliferative expansion of mammary stem cells may contribute to breast cancer initiation, progression, and recurrence.
We hypothesize that denosumab can inhibit RANKL signaling in early breast tumors which express RANK, inhibiting pro-metastatic mechanisms and reducing immunosuppression in the tumor microenvironment. This will be tested in a pre-surgical clinical trial (Phase 0) to evaluate and select the pharmacodynamics markers of RANKL inhibition in breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Denosumab & surgery | Experimental | Biological: denosumab, Procedure: Surgerydenosumab: 120 mg subcutaneous injection Surgery: 2-4 weeks after denosumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must have histologically confirmed invasive breast cancer (stages I-III) who have undergone core needle biopsy (clinically or radiographically at least T1c to allow adequate residual cancer tissue at surgery) and will be scheduled for surgical resection (i.e. segmental excision or mastectomy).
- Archival tissue freshly cut from core biopsy must be available; patients who had a diagnostic core biopsy at an outside institution are eligible as long as it is confirmed that tumor specimens in paraffin blocks (preferred) or ≥ 25 unstained slides, with an associated pathology report, are available.
- Female, Age ≥18 years (pre or postmenopausal).
- Signed informed consent
- Serum calcium or albumin-adjusted serum calcium ≥2.0mmol/L (8.0mg/dL) and ≤ 2.9 mmol/L (11.5mg/dL)
Key exclusion criteria (6 listed)
- Consideration for neoadjuvant therapy
- Serious infections including a history of active Hepatitis B, Hepatitis C or HIV
- Subject has known sensitivity to any of the products to be administered during the study (e.g.., mammalian derived products, calcium, or vitamin D)
- Subject is pregnant or breast feeding, or planning to become pregnant/breastfeed while on study through 5 months after the end of treatment
- Patients have prior history or current evidence of osteonecrosis or osteomyelitis of the jaw, evidence of untreated local gum or oral infection, or non-healed dental or oral surgery
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: Xgevadenosumab: 120 mg subcutaneous injection | Biological | Denosumab & surgery |
| SurgerySurgery: approximately 2-4 weeks after dosing of denosumab | Procedure or surgery | Denosumab & surgery |
Primary outcome
Pharmacodynamic markers of RANKL inhibition determination
Time frame: Change from baseline RANKL inhibition determination at one month
Immunohistochemical analyses (IHC) of RANK and RANKL protein expression will be performed by Clarient Diagnostics Services Inc., Aliso Viejo, CA using prototype assays developed and optimized by Dako on their automated staining platform
1 secondary outcome
Frequency of RANK and RANKL protein expression (by IHC) in operable breast cancer using Immunohistochemical analyses (IHC)
Time frame: Change from baseline frequency of RANK and RANKL protein expression at one month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2020.
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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.
Sylvia Adams, MD principal investigator
NYU Perlmutter Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing denosumab and Surgery in people with Breast Cancer, run by NYU Langone Health at 1 site 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 6 inclusion and 6 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: finished, as of the sponsor's last update on 21 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Pharmacodynamic markers of RANKL inhibition determination (time frame: Change from baseline RANKL inhibition determination at one month). 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 21 Aug 2020.