PALbociclib CoLlaborative Adjuvant Study
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Palbociclib; Standard Adjuvant Endocrine Therapy
Intervention MeSH terms: Palbociclib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5796.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HR+/HER2- breast cancer; Palbociclib

Summary:

      This is a prospective, two arm, international, multicenter, randomized, open-label Phase III
      study evaluating the addition of 2 years of palbociclib to standard adjuvant endocrine
      therapy for patients with HR+ / HER2- early breast cancer (EBC).

      The purpose of the PALLAS study is to determine whether the addition of palbociclib to
      adjuvant endocrine therapy will improve outcomes over endocrine therapy alone for HR+/HER2-
      early breast cancer. Assessment of a variety of correlative analysis, including evaluation of
      the effect of palbociclib in genomically defined tumor subgroups, is planned.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent prior to study specific procedures.

          -  Age ≥18 years (or per national guidelines).

          -  Pre- and postmenopausal women or men with Stage II (Stage IIA limited to max. 1000
             patients) or Stage III early invasive breast cancer

          -  Patients with multicentric and/or multifocal and/or bilateral early invasive breast
             cancer are eligible if all histopathologically examined tumors meet pathologic
             criteria for ER+ and/or PR+ and HER2-.

          -  Patients must have histologically confirmed ER+ and/or PR+, HER2-, early invasive
             breast cancer.

          -  Patients must have undergone adequate (definitive) breast surgery for the current
             malignancy.

        FFPE tumor tissue block must be confirmed to be received at the central sample repository
        prior to randomization.

          -  ECOG performance status 0-1.

          -  Patients must be able and willing to swallow and retain oral medication.

          -  Serum or urine pregnancy test must be negative in premenopausal women within 14 days
             of randomization, or in women with amenorrhea of less than 12 months at time of
             randomization.

          -  Patients who received neo/adjuvant therapy must be after last dose of chemotherapy
             and/or biologic therapy and must have sufficient resolution of side effects.

          -  Patients who received breast/axilla/post-mastectomy chest wall radiotherapy must be
             after last dose of radiotherapy and must have sufficient resolution of side effects.

          -  Patients must have sufficient resolution of any surgical side effects (no active wound
             healing complications).

        -Patients must either be initiating or have already started adjuvant hormonal treatment. -

          -  Patients who already received neo/adjuvant endocrine therapy are eligible as long as
             they are enrolled within 12 months of initial histological diagnosis and after
             completing no more than 6 months of adjuvant endocrine therapy.

          -  Absolute neutrophil count ≥ 1,500/µL

          -  Platelets ≥ 100,000/ mm3

          -  Hemoglobin ≥ 10g/dL

          -  Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin
             within normal range in patients with documented Gilbert's Syndrome.

          -  Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT)
             ≤ 1.5 × institutional ULN.

          -  Serum creatinine below the upper limit of the institutional normal range (ULN) or
             creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels
             above institutional ULN.

        Exclusion Criteria:

          -  Concurrent therapy with other Investigational Products.

          -  Prior therapy with any CDK inhibitor.

          -  Patients with Stage I or IV breast cancer are not eligible.

          -  History of allergic reactions attributed to compounds of chemical or biologic
             composition similar to palbociclib.

          -  Patients receiving any medications or substances that are potent inhibitors or
             inducers of

          -  CYP3A isoenzymes within 7 days of randomization.

          -  Uncontrolled intercurrent illness that would limit compliance with study requirements.

          -  Pregnant women, or women of childbearing potential without a negative pregnancy test
             within 14 days prior to randomization.

          -  Patients with a history of any malignancy are ineligible

          -  Patients who previously received endocrine therapy within 5 years prior to diagnosis
             of the current malignancy.

          -  Patients on antiretroviral therapy.

          -  Patients with clinically significant history of any chronic liver disease.

          -  Patients receiving concurrent exogenous hormone therapy (topical vaginal estrogen
             therapy is allowable).