Two Different Schedules of Palbociclib + Second Line Endocrine Therapy in Estrogen Receptor Positive, HER2 Neg Advanced/Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Palbociclib 100mg; Palbociclib 125mg; Fulvestrant or Tamoxifen or Aromatase Inhibitor
Intervention description: 100mg PO daily; 125mg PO daily 3 weeks out of 4; given at the standard doses/schedules
Intervention MeSH terms: Tamoxifen; Fulvestrant; Palbociclib; Aromatase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 180.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine if the combination of endocrine therapy and
      Palbociclib at a daily dose of 100 mg will result in a better response to therapy with fewer
      dose interruptions than the proposed dosing regimen of 125 mg daily for 21 days out of a 28
      day cycle in combination with endocrine therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Premenopausal and postmenopausal women 18 years of age or older.

          -  Histologically confirmed adenocarcinoma of the breast, with ER positive and HER2
             negative status based on local testing on most recent pathological tumour specimen.

          -  Patients must satisfy the following criteria for prior therapy:

               -  Progressed during treatment or within 12 months of completion of adjuvant
                  endocrine therapy or

               -  Progressed during prior endocrine therapy for advanced/metastatic disease. Note:
                  'Progressed during endocrine therapy' means that the patient progressed while on
                  or within 1 month after discontinuation of endocrine therapy.

          -  One line of chemotherapy for advanced/metastatic disease (regardless of prior adjuvant
             chemotherapy use) is allowed in addition to endocrine therapy.

          -  Patients must have evidence of disease to be eligible for the study, but measurable
             disease is not mandatory.

          -  For those patient with measureable disease who will be included in the response
             assessment, the following criteria must apply:

               -  X-ray ≥ 20 mm

               -  Spiral CT scan or physical exam ≥ 10 mm (lymph nodes must be ≥ 15 mm in the short
                  axis)

               -  Conventional CT scan, MRI ≥ 20 mm

               -  Measurable lesions must be outside a previous radiotherapy field if they are the
                  sole site of disease, unless disease progression has been documented.

        Tumor lesions previously irradiated or subjected to other loco regional therapy will only
        be deemed measurable if progression at the treated site after completion of therapy is
        clearly documented.

          -  Eastern Cooperative Oncology Group (ECOG) 0-2.

          -  Adequate organ and bone marrow function as defined by:

               -  ANC ≥ 1,500/mm3 (1.5 x 109/L)

               -  Platelets ≥ 100,000/mm3 (100 x 109/L)

               -  Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥60 ml/min as
                  calculated using the method standard for the institution;

               -  Total serum bilirubin ≤ 1.5 x ULN (<3 ULN if Gilbert's disease).

          -  Patient must agree to provide tumour tissue from the most recent pathological tumour
             specimen.

          -  Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life
             questionnaires in either English or French

          -  Patient consent must be appropriately obtained in accordance with applicable local and
             regulatory requirements. Each patient must sign a consent form prior to enrollment in
             the trial to document their willingness to participate

          -  Patients must be accessible for treatment and follow up. Patients registered on this
             trial must be treated and followed at the participating centre. This implies there
             must be reasonable geographical limits placed on patients being considered for this
             trial.

          -  In accordance with NCIC CTG policy, protocol treatment is to begin within 2 working
             days of patient randomization.

          -  Women of childbearing potential must have agreed to use a highly effective
             contraceptive method.

        Exclusion Criteria:

          -  Patients with advanced, symptomatic, visceral spread that are at risk of life
             threatening complication in the short term.

          -  Patients with symptomatic CNS involvement, meningeal or parenchymal, that is
             uncontrolled or requires steroids.

          -  Prior treatment with any CDK 4/6 inhibitor.

          -  Prior treatment with mTOR inhibitors.

          -  Active second malignancy, regardless of ongoing treatment.

          -  Any concurrent medical condition that in the opinion of the investigator would
             interfere with the safe administration of the study drug and participation in the
             study.

          -  Participation in a prior anti-cancer investigational study within 30 days prior to
             enrollment.