Efficacy of High Dose Tamoxifen to Advanced Hormone Receptor-High Expressed Breast Cancer
Condition: Breast Cancer Metastatic
MeSH terms: Breast Neoplasms
Intervention: Tamoxifen Oral Product
Intervention description: Tamoxifen 100 mg/d or high-dose Tamoxifen(100 mg/d ) plus chemotherapy
Intervention MeSH terms: Tamoxifen
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: Female
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Breast Cancer; high dose Tamoxifen; endocrine therapy; Hormone Receptor Positive Malignant Neoplasm of Breast; Tamoxifen; Breast Cancer Metastatic

Summary:

      Background: Endocrine therapy is an effective and safe treatment for hormone receptor
      positive breast cancer. Unfortunately , endocrine treatment resistance occurs and there is an
      urgent need for treatment alternative. Laboratory researches and clinical case reports
      indicate that hormone receptor-high expressed breast cancer patients may potentially benefit
      from high-dose Tamoxifen or high-dose Tamoxifen plus chemotherapy , providing a new option
      for treatment strategy.

      Aim: To explore the efficacy and safety of high-dose Tamoxifen to standard hormone
      receptor-high expressed endocrine therapy resisted breast cancer.

      Methods: Eligible patients will be treated with tamoxifen 100 mg/d or high-dose Tamoxifen(100
      mg/d ) plus chemotherapy. Blood and tumor samples will be obtained from the patients.Evaluate
      curative effect every 3 months.

      Primary endpoint: progression-free survival (PFS). Secondary endpoints: objective response
      rate (ORR), clinical benefit rate (CBR), overall survival (OS) and safety.

      Exploratory endpointsincluded the efficacy predictive value of the 18F-FES SUVmax.
    

Eligibility criteria:

        Inclusion Criteria:

        - Female ≥ 18 years, ≤70 years. ECOG 0-1 with no deterioration over previous 2 weeks
        Minimum life expectancy 3 months Histological confirmation of hormone receptor-high
        expressed breast cancer(IHC:ER ≥60% and PR≥60%) on primary tumour at diagnosis/on biopsy of
        metastasis Histological confirmation of HER2 negative breast cancer on primary tumour at
        diagnosis/on biopsy of a metastasis The disease-free time of relapsed patients is more than
        12 months Once received standard hormone treatment and progressed Clinical or histological
        confirmation of metastatic or locally advanced disease not amenable to curative surgical
        resection At least one evaluative focus according to RECIST creterion or non-measurable
        disease but only bone metastasis Adequate bone marrow and organ function Progressive
        disease whilst receiving endocrine therapy for locally advanced or metastatic BC or
        relapsed with metastatic disease whilst receiving endocrine therapy Radiological or
        objective clinical evidence of recurrence or progression on or after last systemic therapy
        prior to enrolment

          -  4 prior lines of endocrine therapy for ABC

          -  3 line of cytotoxic chemotherapy for ABC Suitable for further endocrine therapy
             Availability of archival tumour sample or fresh biopsy Informed consent Normal organ
             function

        Exclusion Criteria:

          -  Last dose chemotherapy, immunotherapy targeted therapy, biological therapy or tumour
             embolisation <21 days prior to study treatment Last dose of palliative radiotherapy <7
             days prior to study treatment Rapidly progressive visceral disease not suitable for
             further endocrine therapy Spinal cord compression or brain/meningeal metastases unless
             asymptomatic, treated and stable and not requiring steroids for ≥ 4 weeks study
             treatment Creatinine clearance <30 ml/min. Patients with creatinine clearance <50
             mL/min will start at a permanently reduced vandetanib dose of 200 mg.

        Major surgery (excluding placement of vascular access) within 4 weeks before study
        treatment Evidence of severe or uncontrolled systemic diseases, including uncontrolled
        hypertension, active bleeding diatheses, or active infection including hepatitis B,
        hepatitis C and HIV With the exception of alopecia, any unresolved toxicities from previous
        therapy greater than CTCAE grade 1 before study treatment Elevated ALP in absence of bone
        metastasis Evidence of dementia, altered mental status or any psychiatric condition that
        would prohibit understanding or rendering of informed consent Participation in another
        study with investigational product during last 30 days Inability or unwillingness to comply
        with study procedures, including inability to take regular oral medication