Denosumab in Treating Patients With ER and/or PR Positive, HER2 Negative Metastatic Breast Cancer With Bone Metastases and Detectable Circulating Tumor Cells
Condition: Breast Carcinoma Metastatic in the Bone; Circulating Tumor Cell Count; Estrogen Receptor Positive; HER2/Neu Negative; Progesterone Receptor Positive; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms; Neoplastic Cells, Circulating
Intervention: Denosumab; Laboratory Biomarker Analysis
Intervention description: Given SC; Correlative studies
Intervention MeSH terms: Denosumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to look at the amount of cancer cells in the blood of
      participants who are being treated with denosumab. The other purpose is to look at how long
      it takes for cancer to get worse when participants are being treated with denosumab.
      Circulating tumor cells (CTCs) in the blood of patients with metastatic breast cancer (MBC)
      have been associated with shorter survival than when CTCs are absent, especially in patients
      whose cancer has spread to their bones. In this study, we want it see if denosumab (the study
      drug) will decrease the number of CTCs measured in patients with MBC and cancer that has
      spread to their bones. We also plan to get blood from participants to study other research
      markers of interest.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed ER and/or PR positive,
             HER-2/neu negative metastatic breast cancer; they can be enrolled in any line of
             therapy without investigational agents and should have stable disease or a partial
             response (which can be determined clinically) on current systemic treatment; patients
             must also have pathologic OR radiographic evidence of bone metastases and >= 5 CTCs;
             (Note: the pathology report that is used by the physician to determine diagnosis, will
             be used to determine patient eligibility; ER and PR status should be available at the
             time of registration)

          -  Patients may have either measurable or non-measurable within 30 of days of
             registration; (lesions treated with radiation therapy must not be used as a target
             lesion); (Note: per Response Evaluation Criteria in Solid Tumors [RECIST] criteria
             version [v.] 1.1, measurable disease is defined as at least one lesion that can be
             accurately measured in at least one dimension; non-measurable disease is defined as
             all other lesions, including small lesions [longest diameter < 10 mm or pathological
             lymph nodes with P10 to < 15 mm short axis] as well as truly non-measurable lesions;
             lesions considered truly nonmeasurable include: leptomeningeal disease, ascites,
             pleural or pericardial effusion, and inflammatory breast disease, lymphangitic
             involvement of skin or lung, abdominal masses/abdominal organomegaly identified by
             physical exam that is not measurable by reproducible imaging techniques)

          -  Patients may be enrolled in any line of standard treatment (without investigational
             agents); the start date of current treatment should be at least two 2 weeks or more
             prior to registration; (Note: patients will continue to receive the planned active
             treatment with chemotherapy or endocrine therapy [standard of care] and initiate
             denosumab at the recommended dose for this protocol)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Leukocytes >= 3,000/mcL (without growth factor)

          -  Platelets >= 100,000/mcL (with or without transfusion)

          -  Hemoglobin >= 8 (with or without transfusion)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (serum
             glutamic-oxaloacetic transaminase [SGOT] and serum glutamate pyruvate transaminase
             [SGPT]) =< 2.5 times institutional upper limit of normal (for patients with liver
             metastasis up to =< 5 times of upper limit of normal [ULN] is allowed)

          -  Bilirubin =< 1.5 ULN (for patients with liver metastasis up to =< 5 times of ULN is
             allowed)

          -  Serum creatinine =< 1.5 ULN

          -  Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above
             institutional normal (creatinine clearance should be calculated per institutional
             standard)

          -  Patients must have a serum calcium of >= 2.0 mmol/L (8.0 mg/dL) or albumin-adjusted
             serum calcium =< 2.9 mmol/L (11.5 mg/dL) within 30 days of registration; (Note: if
             patients are undergoing treatment for hypocalcemia and the serum calcium value at
             screening is > 8.0 mg/dl, then the patient will be eligible for this study)

          -  Females of child-bearing potential (FOCBP) and males with his or her partner must
             agree to use two acceptable methods of effective contraception, at study entry, for
             the duration of study participation, and for 5 months following completion of therapy;
             subjects who are surgically sterile (e.g., history of bilateral tubal ligation,
             hysterectomy) or whose sexual partner is sterile (e.g., history of vasectomy) are not
             required to use additional contraceptive measures; should a female patient become
             pregnant or suspect she is pregnant while participating in this study, she should
             inform her treating physician immediately; likewise, if a male patient impregnates his
             female partner, he should inform the treating physician immediately; NOTE: a FOCBP is
             any woman (regardless of sexual orientation, having undergone a tubal ligation, or
             remaining celibate by choice) who meets the following criteria:

               -  Has not undergone a hysterectomy or bilateral oophorectomy

               -  Has had menses at any time in the preceding 12 consecutive months (and therefore
                  has not been naturally postmenopausal for > 12 months)

          -  FOCBP must have a negative serum OR urine pregnancy test =< 7 days prior to
             registration

          -  Ability to understand and willingness to sign a written informed consent and Health
             Insurance Portability and Accountability Act (HIPAA) consent document prior to
             registration

          -  Willingness and ability of subject to comply to study requirements

        Exclusion Criteria:

          -  Patients may not be receiving any other investigational agents; a 2 week washout
             period for investigational agents is required before registration

          -  Patients with clinically symptomatic brain metastases or who required treatment for
             brain metastases within 4 weeks of registration (stable sequelae acceptable if
             treatment has been completed; these lesions cannot be used as target lesions)

          -  Patients who have a history of allergic reactions attributed to compounds of similar
             chemical or biologic composition to denosumab are not eligible (i.e. same class of
             drugs) (Note: prior bisphosphonates are allowed; patients could have received
             bisphosphonates or be bisphosphonate-naive; patients who were previously on
             bisphosphonates can be enrolled in the study, as long as they have a wash-out period
             of 2 weeks prior to registration)

          -  Patients who are on corticosteroids or immunosuppressant's are not eligible; a 2 week
             wash-out period for is required before registration

          -  Patients who have a known additional malignancy that is progressing or requires active
             treatment are not eligible; patients who have had a prior diagnosis of cancer and if
             it has been < 3 years since their last treatment are also not eligible; NOTE:
             exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer

          -  Patients who have an uncontrolled intercurrent illness including, but not limited to
             any of the following, are not eligible:

               -  Hypertension (defined as 160/90 mmHg for 3 consecutive readings 2-5 mins apart)
                  that is not controlled on medication

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

               -  Any other illness or condition that the treating investigator feels would
                  interfere with study compliance or would compromise the patient's safety or study
                  endpoints

          -  Subject is pregnant or breast feeding, or planning to become pregnant within 5 months
             after the end of treatment

          -  Known human immunodeficiency virus (HIV)-positive patients who are on combination
             antiretroviral therapy; (this is because of the potential for pharmacokinetic
             interactions with denosumab)

          -  No known prior history or current evidence of osteonecrosis/osteomyelitis of the jaw

          -  No known prior history or current evidence of untreated local gum or oral infection

          -  No known/planned active dental or jaw condition which requires oral surgery, including
             tooth extraction

          -  No known non-healed dental/oral surgery, including tooth extraction

          -  Patients have planned invasive dental procedures during the course of the study