PALbociclib CoLlaborative Adjuvant Study: A Randomized Phase III Trial of Palbociclib With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone for Hormone Receptor Positive (HR+) / Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Early Breast Cancer (PALLAS)

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 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 within normal institutional limits 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 (for exceptions see: Pallas -

• Protocol, v1.0, Exclusion criteria 8).
• Patients who previously received endocrine therapy within 5 years prior to diagnosis of the current malignancy.
• Patients on combination antiretroviral therapy.
• Patients with clinically significant history of any liver disease.
• Patients receiving concurrent exogenous hormone therapy (topical vaginal estrogen therapy is allowable).