Denosumab in Treating Patients With Stage I-III Breast Cancer

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Basic Trial Information

PhaseTypeAgeTrial IDs
No phase specifiedTreatment18 and over117527
NCI-2012-02802, NCT01545648

Trial Description

Summary

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

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

I. To evaluate the correlation of DTC at each time point with breast cancer recurrence in patients on this study.

TERTIARY OBJECTIVES:

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.

OUTLINE:

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.

Eligibility Criteria

Inclusion Criteria:

Total bilirubin within normal limits (elevation of total bilirubin due to Gilbert’s disease is allowed)

Patients who have had surgery following neoadjuvant chemotherapy or hormonal therapy are eligible to participate in this trial

Patients with histologically or cytologically confirmed stage I, II, or III breast cancer

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

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

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

Prior therapy:

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

Exclusion Criteria:

Karnofsky performance status < 90%

Pregnant or lactating women and women of child-bearing potential who are not using an effective method of birth control

A history of human immunodeficiency virus (HIV) infection

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

Severe, concurrent illness that would likely prevent the patient from being able to comply with the study protocol

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
Jiali li, Principal Investigator

Trial Sites

U.S.A.

California
San Francisco

UCSF Medical Center-Mount Zion

Jiali li
Ph: 877-827-3222
Email: Jiali.li@ucsf.edu

Jiali li
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer 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.