Denosumab in Treating Patients With Stage I-III Breast Cancer
Basic Trial Information
|Phase II||Treatment||Active||18 and over||117527|
This pilot clinical trial studies denosumab in treating patients with stage I-III breast cancer. Monoclonal antibodies, such as denosumab, can block tumor growth in different ways. Some block the ability of tumors to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
Further Study Information
I. To determine the reduction of bone marrow disseminated tumor cells (DTC) as measured by immunomagnetic enrichment (IE)/flow cytometry (FC) at 6 and 12 months compared to baseline in patients with early stage breast cancer treated with denosumab.
I. To evaluate the correlation of DTC at each time point with breast cancer recurrence in patients on this study.
I. To evaluate biomarkers in the bone marrow microenvironment. Evaluate novel biomarkers of metastatic progression in separated DTC and in hematopoietic cells in patients with early stage breast cancer, including:
* Genes that promote osteolysis of the bone: Receptor activator of nuclear factor-kB ligand (RANK), RANKL, tumor receptor associated factor (TRAF)6, transforming growth factor (TGF)-beta, and bone morphogenetic protein (BMP)2.
* Gene expression of inflammatory cytokines and immune markers: Colony stimulating factor (CSF)-1, interleukin (IL)-8, IL-17, CD 47, signal-regulatory protein alpha (SIRPA), and tumor necrosis factor (TNF)-alpha.
* RANKL level in the serum and bone marrow at study entry, 6 months and 12 months.
Patients receive denosumab subcutaneously (SC) monthly for 6 months, and then every 12 weeks for 1 year.
After completion of study treatment, patients are followed up at 6 and 12 months.
Patients with histologically or cytologically confirmed stage I, II, or III breast cancer
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Prior adjuvant therapy is not required for participation in this study
If adjuvant or neoadjuvant treatment with chemotherapy is recommended, it must be completed before study start, and not more than 18 months prior to study start
If adjuvant or neoadjuvant treatment with trastuzumab (Herceptin) is recommended, patients should have received at least 3 months of therapy before eligibility bone marrow is performed
Patients who have had surgery following neoadjuvant chemotherapy or hormonal therapy are eligible
Patients must have completed definitive surgery and have completely resected disease
Concomitant hormonal therapy is allowed
If adjuvant hormonal treatment is recommended, patients should have received at least 3 months of therapy before screening bone marrow is performed
Bone marrow aspirate positive by IE/FC assay within 12 weeks of study entry
Definition of positive: > 10 DTC/ml
Timing of bone marrow aspiration to determine study eligibility
- If patient is to receive either no adjuvant therapy or hormonal therapy alone, the aspiration may be performed at diagnosis as part of the large micrometastasis study at University of California San Francisco (UCSF), or following diagnosis if the patient received initial surgery elsewhere; this is also true for patients who have surgery following neoadjuvant therapy for breast cancer
- If the patient is to receive adjuvant chemotherapy, the aspiration will be performed at least three weeks after chemotherapy has been completed
- For trastuzumab and hormone therapy, see above
Total bilirubin within normal limits (elevation of total bilirubin due to Gilbert’s disease is allowed)
Alkaline phosphatase within normal limits
Aspartate aminotransferase (AST) within normal limits
Calculated creatinine clearance (calculated glomerular filtration rate [GFR]) > 30 ml/min
Ability to understand and sign informed consent
Patients who have had surgery following neoadjuvant chemotherapy or hormonal therapy are eligible to participate in this trial
Karnofsky performance status < 90%
Patients participating in this study are not allowed to receive bisphosphonate therapy during the study period, either oral or intravenous
Patients who completed adjuvant or neoadjuvant therapy more than 18 months prior to study screening
A history of malignancy within the last 5 years except basal cell carcinoma of skin
A history of human immunodeficiency virus (HIV) infection
Severe, concurrent illness that would likely prevent the patient from being able to comply with the study protocol
Pregnant or lactating women and women of child-bearing potential who are not using an effective method of birth control
Significant dental disease that requires major intervention during the study period, such as tooth extraction
Significant coagulopathy that would prevent safe bone marrow aspiration
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
UCSF Medical Center-Mount Zion
- National Cancer Institute
UCSF Medical Center-Mount Zion
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01545648
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.