To Reverse ENDocrine Resistance Trial - PD 0332991 Monotherapy vs PD 0332991 in Combination With the Endocrine Therapy

Phase 2,Open-label,Multicenter,Randomized Study of PD0332991 (Oral CDK4/6 Inhibitor) Monotherapy and in Combination With the HT to Which the pt Has Progressed in the Previous Line for ER+,Her2- Post-menopausal Advanced Breast Cancer Pts

This study aims to assess the activity of PD0332991 in monotherapy and in combination with the endocrine therapy (anastrozole, letrozole, exemestane or fulvestrant) on which the patient has progressed in the previous line for advanced breast cancer in order to reverse endocrine resistance.

In a clinical context, there is a lack of molecular compounds with demonstrated clinical activity in delaying/reversing resistance to endocrine agents. CDK 4/6 inhibitors may represent a biologically-driven option in this context.

With the present study investigators aim to complement the ongoing trial on PD0332991 by acquiring information on its clinical activity in post-menopausal patients with ER positive, Her2 negative advanced breast cancer patients already pretreated with a first-line or second line endocrine therapy.

Inclusion Criteria:

• Histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease
• ER positive tumor ≥ 10%
• HER2 negative breast cancer by FISH or IHC
• Progression of advanced breast cancer on first or second line endocrine therapy for advanced breast cancer
• Paraffin-embedded tumor available for centralized assessment of biomarkers
• Measurable disease according to RECIST 1.1 (bone only disease is allowed only if measurable).
• Postmenopausal status
• Eastern Cooperative Oncology Group (ECOG) Performance status 0 -2
• Resolution of all acute toxic effects of prior therapy or surgical procedures to CTCAE grade >1
• Adequate organ function

Exclusion Criteria:

• Unstable brain metastases
• Prior treatment with more than one line of CT or more than two lines of HT advanced breast cancer or any CDK inhibitor
• Current treatment with therapeutic doses of anticoagulant
• Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors / inducers, drugs that are predominantly metabolized by CYP3A with narrow therapeutic indices, drugs with the potential of prolonging QT interval
• Diagnosis of any secondary malignancy within the last 3 years
• Active inflammatory bowel disease or chronic diarrhea
• Known human immunodeficiency virus infection; active hepatitis C, active hepatitis B