Denosumab for Breast Cancer With Bone Mets
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Denosumab
Intervention description: 120 mg subcutaneously on Day 1 of every 28 day cycle.
Intervention MeSH terms: Denosumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast cancer; Breast carcinoma; Bone metastasis; Cancer that has spread to the bone; Denosumab; AMG 162; Prolia; Hormonal agent

Summary:

      The goal of this clinical research study is to learn if denosumab in combination with a
      hormonal drug can help lower the number of circulating tumor cells (CTCs) in patients with
      breast cancer that has spread to the bone. The safety of this combination will also be
      studied.

      This is an investigational study. Denosumab is FDA approved and commercially available to
      prevent bone-related events caused by breast cancer that has spread to the bone. Using
      denosumab to lower CTCs in patients with breast cancer that has spread to the bone is
      investigational.

      You may have the option of continuing denosumab after the study ends.

      Up to 35 patients will take part in this study. All will be enrolled at MD Anderson.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients have histological confirmation of breast carcinoma.

          2. Patients have progressive metastatic disease with predominantly bone metastasis with 1
             or more lesions and at least 1 bone lesion has pathological confirmation, have not
             been treated or have been treated with any prior therapies (including bisphosphonate
             treatment and/or radiation therapy). Patients can have soft tissue involvement (Lymph
             node and skin) and/or metastatic lesions at major organ sites (i.e. lung, liver, etc).

          3. Patients have positive ER expression in the primary tumor site by IHC (defined as
             >/=10%) (PR status is not required)

          4. Adequate hematologic function: 1)Absolute neutrophil count (ANC) >/= 1.0 x 10^9/L, 2)
             Platelet count >/= 50 x 10^9/L, 3) Hemoglobin >/= 9.0 g/dL

          5. Adequate cardiac function (LVEF >/= 45%) if patient has known cardiac dysfunction
             history

          6. Adequate Renal function: Calculated creatinine clearance >30 ml/min

          7. Adequate Hepatic function: 1) Aspartate aminotransferase (AST) </= 2.5 x ULN; 2)
             Alanine aminotransferase (ALT) </= 2.5 x ULN; 3) Alkaline phosphatase (Alp) </= 2.5 x
             ULN; 4) Total bilirubin </= 2.0 x ULN

          8. Serum calcium or albumin-adjusted serum calcium >/=2.0mmol/L (8.0mg/dL) and </= 2.9
             mmol/L (11.5mg/dL)

          9. Patients have ability and willingness to sign written informed consent.

         10. Patients are 18 years of age or older.

         11. Female patients of childbearing potential (A female not free from menses > 2 years or
             not surgically sterilized) must be willing to use highly effective contraception to
             prevent pregnancy or agree to abstain from heterosexual activity throughout the study.
             Highly effective contraception, defined as male condom with spermicide, diaphragm with
             spermicide, intra-uterine device. Highly effective contraception must be used by both
             sexes during the study and must be continued for 5 months after the last dose of
             denosumab.

         12. Female patients of childbearing potential must have negative serum pregnancy test </=
             21 days prior to starting study treatment.

         13. Patients have CTC >/=3.

        Exclusion Criteria:

          1. Patients have known sensitivity to any of the products to be administered during the
             study (e.g., mammalian derived products, calcium, or vitamin D).

          2. Patients receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy,
             radiation therapy and biological therapy) while taking study medication. However,
             patients receiving CDK4/6 inhibitor or mTOR inhibitor as a standard of care while on
             study is permitted.

          3. Patients with metastatic sites that requires chemotherapy.

          4. Patients with active infection and requiring IV or oral antibiotics.

          5. Patients with concurrent disease or condition that would make them inappropriate for
             study participation, or any serious medical disorder that would interfere with
             patients' safety.

          6. Patients have HER2-positive breast carcinoma (IHC staining more than 3+ or HER2 gene
             amplification by FISH)

          7. Patient is pregnant or breast feeding, or planning to become pregnant within 5 months
             after the end of treatment.

          8. Patient is of child bearing potential and is not willing to use, in combination with
             her partner, two highly effective methods of contraception or abstinence during
             treatment and for 5 months after the end of treatment.

          9. Male patients.

         10. Patients have prior history or current evidence of osteonecrosis/osteomyelitis of the
             jaw.

         11. Patients have active dental or jaw condition which requires oral surgery, including
             tooth extraction.

         12. Patients have non healed dental/oral surgery, including tooth extraction.

         13. Patients planned invasive dental procedures.

         14. Patients experiencing a visceral crisis including severe organ dysfunction as assessed
             by > Gr 2 symptomatic toxicities, laboratory studies, and/ or rapid progression of
             disease originating from visceral metastasis.

         15. Patients that have received the study medication (Xgeva/Prolia).