Neoadjuvant Hormonal Therapy Plus Palbociclib in Operable, Hormone Sensitive and HER2-Negative Primary Breast Cancer

Exclusion Criteria

• •1. Male
• •2. Locally advanced breast cancer ( Any T4 or Any N2, N3), or distant metastasis
• •3. Multicentric breast cancer (Note: Multifocal breast cancer,located in one quadrant/are is eligible)
• •4. Prior treatment with chemotherapy, radiotherapy and/or endocrine therapy
• •5. Previous use of SERMs such as raloxifene.
• •6. Prior therapy with any CDK4/6 inhibitor or with everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway.
• •7. Prior history of other malignancy within 5 years of study entry, aside from basal cell carcinoma of the skin or carcinoma-in-situ of the uterine cervix
• •8. Major surgery within 3 weeks of first study treatment
• •9. Patients treated within the last 7 days prior to randomization with:
• •* Food or drugs that are known strong and moderate CYP3A4 inhibitors (e.g., amprenavir, aprepitant, atazanavir, boceprevir, casopitant, cimetidine, ciprof-loxacin, clarithromycin, conivaptan, cobicistat, crizotinib, cyclosporine, da-runavir, diltiazem, dronedarone, elvitegravir, erythromycin, fluconazole, fosamprenavir, imatinib, indinavir, isavuconazole, istradefylline, itraconazole,ketoconazole, letermovir, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, nilotinib, posaconazole, ritonavir, saquinavir, schisandra sphenan-thera extract, telaprevir, telithromycin, tofisopam, verapamil, voriconazole, and grapefruit, grapefruit juice or any product containing grapefruit);
• •* Drugs that are known strong and moderate CYP3A4 inducers (e.g., bosentan, carbamazepine, efavirenz, etravirine, modafinil, phenobarbital, phenytoin, ri-fampin, rifapentin, and St. John's wort);
• •10. Any of the following in the previous 6 months of randomization: myocardial in-farction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 4.03 grade ≥ 2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident in-cluding transient ischemic attack, or symptomatic pulmonary embolism
• •11. Family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
• •12. Uncontrolled electrolyte disorders (eg, hypocalcemia, hypokalemia, hypomag-nesemia) that can compound the effects of a QTc-prolonging drug.
• •13. Active inflammatory bowel disease or chronic diarrhea. Short bowel syndrome. Upper gastrointestinal surgery including gastric resection.
• •14. Prior hematopoietic stem cell or bone marrow transplantation.
• •15. Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding subcutaneous injections of leuprorelin or goserelin.
• •16. Hepatitis B and/or hepatitis C carriers (Patients with HBsAg+ or HBV-DNA+ who need antiviral treatment during any anti-cancer therapy based on guidelines are excluded even if the patient's hepatic function is normal. Patients with HCVAb+, whose HCV-RNA is positive (+) are excluded.)
• •17. Known human immunodeficiency virus (HIV) infection
• •18. Known hypersensitivity to anti-aromatase drugs, tamoxifen or any cell cycle in-hibitor.
• •19. Patients who are pregnant or lactating. Patients of childbearing potential and/or her partner who are unwilling or unable to use a method of highly effective non-hormonal contraception throughout the study and continue for at least 21 days in patients after the last dose of investigational drug.
• •20. Other severe acute or chronic medical or psychiatric condition, or laboratory ab-normality that would impart, in the judgment of the investigator, excess risk as-sociated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
• •21. Patients who are investigational site staff members or relatives of those site staff OOTR-N016/KBCRN-B-003/HT-PAB Protocol (version 1.2 dated Oct 11, 2018) 24 members or patients who are the sponsor employees directly involved in the con-duct of the trial.
• •22. Participation in other studies involving investigational drug (s) (Phases 1-4) within 2 weeks before randomization and/or until a visit at 4 weeks (+7 days) after operation.