Pilot Study to Evaluate the Impact of Denosumab on Disseminated Tumor Cells (DTC) in Patients With Early Stage Breast Cancer
Condition: Early Stage Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Denosumab
Intervention description: Formulation of Dosage forms
The vial presentations of denosumab contain 60 mg/mL denosumab, 17 mM sodium acetate, and 4.7% (w/v) sorbitol, at a pH of 5.2, filled to a target deliverable volume of 1.0 mL; or 70 mg/mL denosumab, 18 mM sodium acetate and 4.6% (w/v) sorbitol, at a pH of 5.2, filled to a target deliverable volume of 1.7 mL. The prefilled syringe (PFS) drug product contains denosumab at 60 mg/mL, 17 mM sodium acetate, 4.7% (w/v) sorbitol, and 0.01% (w/v) polysorbate 20, at a pH of 5.2, filled to a target deliverable volume of 1.0 mL.
Dosage: 120 mg, monthly for total of 6 months, then every 12 weeks for 2 doses, for a total treatment course of one year
Route of administration: subcutaneous injection
Intervention MeSH terms: Denosumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: breast; cancer; early; DTC; disseminated; tumor; cells

Summary:

      The purpose of this study is to see whether taking denosumab for 12 months in women with a
      significant number of disseminated tumor cells in the bone marrow can reduce the number of
      these cells below a significant level.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients ≥18 years of age with histologically or cytologically confirmed stage I, II,
             or III breast cancer.

          2. ECOG Performance Status of 0 or 1

          3. Prior therapy:

               1. Prior adjuvant therapy is not required for participation in this study.

               2. 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.

               3. 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.

               4. Patients who have had surgery following neoadjuvant chemotherapy or hormonal
                  therapy are eligible

               5. Patients must have completed definitive surgery and have completely resected
                  disease.

               6. Concomitant hormonal therapy is allowed.

               7. Concomitant adjuvant trastuzumab is permitted

               8. If adjuvant hormonal treatment is recommended, patients should have received at
                  least 3 months of therapy before screening bone marrow is performed.

          4. Bone marrow aspirate positive by IE/FC assay within 12 weeks of study entry

               1. Definition of positive: >10 DTC/ml

               2. Timing of bone marrow aspiration to determine study eligibility

             i.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
             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.

             ii.If the patient is to receive adjuvant chemotherapy, the aspiration will be
             performed at least three weeks after chemotherapy has been completed.

             iii.For trastuzumab and hormone therapy, see above.

          5. Laboratory studies

               1. Liver function tests within normal limits, including total bilirubin, alkaline
                  phosphatase, and AST (elevation of total bilirubin due to Gilbert's disease is
                  allowed).

                    -  Gilbert's disease: a common hereditary cause of increased indirect
                       bilirubin, but with normal direct bilirubin.

               2. Calculated creatinine clearance (calculated GFR) > 30 ml/min

          6. Ability to understand and sign informed consent

          7. Patients who have had surgery following neoadjuvant chemotherapy or hormonal therapy
             are eligible to participate in this trial.

        Exclusion Criteria:

          1. Karnofsky performance status < 90%

          2. Patients participating in this study are not allowed to receive bisphosphonate therapy
             during the study period, either oral or intravenous.

          3. Patients who completed adjuvant or neoadjuvant therapy more than 18 months prior to
             study screening.

          4. A history of malignancy within the last 5 years except basal cell carcinoma of skin.

          5. A history of human immunodeficiency virus (HIV) infection.

          6. Severe, concurrent illness that would likely prevent the patient from being able to
             comply with the study protocol.

          7. Pregnant or lactating women and women of child-bearing potential who are not using an
             effective method of birth control.

          8. Significant dental disease that requires major intervention during the study period,
             such as tooth extraction

          9. Significant coagulopathy that would prevent safe bone marrow aspiration