Presurgical Trial of Denosumab in Breast Cancer
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|ClinicalTrials.gov Identifier: NCT02900469|
Recruitment Status : Completed
First Posted : September 14, 2016
Last Update Posted : August 21, 2020
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Biological: denosumab Procedure: Surgery||Early Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pre-surgical Evaluation of Denosumab in Patients With Operable Invasive Breast Cancer|
|Study Start Date :||October 2016|
|Actual Primary Completion Date :||December 3, 2019|
|Actual Study Completion Date :||January 3, 2020|
Experimental: Denosumab & surgery
denosumab: 120 mg subcutaneous injection
Surgery: 2-4 weeks after denosumab
denosumab: 120 mg subcutaneous injection
Other Name: Xgeva
Surgery: approximately 2-4 weeks after dosing of denosumab
- 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
- 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 ]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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02900469
|United States, New York|
|NYU Perlmutter Cancer Center|
|New York, New York, United States, 10016|
|Principal Investigator:||Sylvia Adams, MD||NYU Perlmutter Cancer Center|