Effect of Zoledronic Acid as Anti-Cancer Treatment in Metastatic Breast Cancer Patients
Condition: First or Second Line HER2-negative Breast Cancer; Metastatic Disease Without Bone Metastasis
MeSH terms: Breast Neoplasms; Neoplasm Metastasis; Bone Neoplasms; Bone Marrow Diseases
Intervention: Zoledronic acid; Standard Therapy
Intervention description: Patients with no bone metastasis (n=150) will receive Standard therapy plus Zoledronic acid administration 4 mg IV monthly during Months 1-18.; Standard Therapy, including chemotherapy and hormonal therapy, was determined at the discretion of the investigator.
Intervention MeSH terms: Zoledronic Acid; Diphosphonates
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HER2-negative; HER2; Metastatic breast cancer; First Line breast cancer; Second Line breast cancer; Breast cancer; Metastatic; Stage IV breast cancer; Progression free survival; PFS; Circulating Tumor Cells; CTCs; Zoledronic acid; HER2-negative metastatic breast cancer patients without bone metastasis

Summary:

      This study will evaluate zoledronic acid's anti-cancer effects and Circulating Tumor Cell
      (CTCs) measurements in patients with HER2-negative metastatic breast cancer without bone
      metastasis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent

          -  Female patients (age ≥18 years)

          -  HER2-negative metastatic breast cancer (stage IV)

          -  Patients will be receiving chemotherapy or hormonal therapy

          -  Patients with no bone metastasis and ≤1 prior treatments for metastatic breast cancer.
             Patients with newly diagnosed metastatic breast cancer may have received adjuvant or
             neoadjuvant chemotherapy as long as treatment was completed ≥12 months prior to
             relapse.

          -  Asymptomatic brain metastasis is permitted if all of the following criteria are met:

               1. no sign of clinical progression or known progression of brain metastasis

               2. off steroids for at least 2 weeks prior to study enrollment

          -  Stable renal function: two serum creatinine determinations of <3 mg/dL, obtained no
             less than 7 days apart (one value may be obtained within 6 weeks prior to Screening;
             the second must be obtained during Screening)

          -  ECOG performance status of 0 or 1

          -  Life expectancy of ≥ 6 months

          -  Negative serum pregnancy test

          -  Ability and willingness to comply with all study requirements

        Exclusion Criteria:

          -  Known hypersensitivity to zoledronic acid or other bisphosphonates

          -  Patients with history of another malignancy within the last two years prior to study
             enrollment, except cured basal cell carcinoma of the skin or excised carcinoma in site
             of the cervix

          -  Use of concurrent investigational agents is prohibited. Prior use of investigational
             agents is permitted if discontinued ≥30 days prior to Screening.

          -  No prior therapy with an antiresorptive agent

          -  Patients with active brain metastases or meningeal metastases

          -  Current or recent (in the six months prior to initial study drug treatment) severe
             cardiovascular disease (defined as uncontrolled congestive heart failure),
             hypertension refractory to treatment, or poorly controlled Type I/II diabetes mellitus

          -  Current active dental problems including dental abscess or infection of the jawbone
             (maxilla or mandible) or a current or prior diagnosis of osteonecrosis of the jaw

          -  Patients who have received radiotherapy ≤ 4 weeks prior to study enrollment or who
             have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for
             bone lesions ≤ 2 weeks prior to study enrollment is allowed

          -  Patients who have undergone major surgery (e.g., intra-thoracic, intra-abdominal or
             intra-pelvic) ≤ 4 weeks prior to study enrollment or who have not recovered from side
             effects of such therapy

          -  Diminished renal capacity: calculated creatinine clearance (CrCl) <30 mL/min (based on
             Cockcroft-Gault formula)

          -  Corrected (i.e., adjusted for serum albumin) serum calcium of <8.0 mg/dL (2.00 mmol/L)
             or ≥ 12 mg/dL (3.00 mmol/L)

          -  Pregnant or breast-feeding females

          -  Women of child-bearing potential who are not willing/able to use effective methods of
             birth control (e.g., abstinence, oral contraceptives or implants, IUD, vaginal
             diaphragm or sponge, or condom with spermicide)

          -  History of non-compliance to medical regimens and/or patients who are considered
             unreliable

          -  History of bone metabolism diseases