Study Drug Administration:
If you are found to be eligible to take part in this study, you will receive denosumab
through a needle under your skin on Day 1 of each 28-day study cycle.
Starting on Day 1 of week 4, you will also begin taking a hormonal drug. The study doctor
will choose the hormonal drug you receive based on your previous hormonal therapy for breast
cancer. The study doctor will give you instructions for taking your hormonal drug.
Study Visits:
On Day 1 of week 4:
- You will have a physical exam
- Blood (about 3 tablespoons) will be drawn for routine tests
- Blood (about 5 teaspoons) will be drawn for CTC testing and to check your immune
system.
- Urine will be collected to test for a biomarker that is used to measure the rate of
bone breakdown.
- If the study doctor thinks it is needed, you will have a PET scan, a bone scan, or an
MRI to check the status of the disease.
On Day 1 of Cycle 2 and Cycle 3, blood (about 1 teaspoon) will be drawn for routine tests.
Length of Study:
You may receive the denosumab and hormonal therapy combination for up to 13 weeks. You will
be taken off study if the disease gets worse or intolerable side effects occur.
End of Study Visit:
After your last dose of the study drug, the following tests and procedures will be
performed:
- You will have a physical exam.
- Blood (about 3 tablespoons) will be drawn for routine tests.
- Blood (about 5 teaspoons) will be drawn for CTC testing and to check your immune
system.
- Urine will be collected to test for a biomarker that is used to measure the rate of
bone breakdown.
- If the study doctor thinks it is needed, you will have a PET scan, a bone scan, or an
MRI to check the status of the disease.
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.
Up to 35 patients will take part in this study. All will be enrolled at MD Anderson.
Inclusion Criteria:
1. Patients have histological confirmation of breast carcinoma.
2. Patients have metastatic disease with predominantly bone metastasis with 2 or more
lesions and have not been treated. 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%)
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 inhibitor while on study is permitted.
3. Patients with metastatic sites that requires chemotherapy and/or non-hormonal
targeted therapy.
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.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Female
