In Untreated Women with Operable, HR-positive and HER2-negative Breast Cancer
Conditions
Interventions
Intervention type:DRUG
Name of intervention:hormonal therapy plus palbociclib
Dose form / Japanese Medical Device Nomenclature:CAPSULE
Route of administration / Site of application:ORAL
Dose per admin
Sponsors
Kyoto Breast Cancer Research Network
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1.Pre/peri- or post-menopausal women 18 years and older (or local legal age, whichever is higher) 2.Primary tumor greater than 15 mm in diameter 3.Histologically proven invasive breast cancer 4.Positive hormone receptor (ER and/or PgR >= 1% in proportion of positive staining score) 5.Negative HER-2 receptor 6.Ki67 index equal to or greater than 14% (Ki67 >= 14%) by centr 7.Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 1,500/mm3 Platelets: >= 100,000/mm3 Hemoglobin: >= 9 g/dL Bilirubin: <= 1.5 x upper limits of normal (ULN) Serum Creatinine: <= 1.5 x ULN Alkaline phosphatase: <= 2 x ULN Alkaline phosphatase: <= 2 x ULN AST and ALT: <= 2 x ULN Cardiac function: Normal finding of Electrocardiogram (ECG),QTc <= 480 msec (based on the mean value of the triplicate ECGs). 10.Able to give written informed consent form 11.Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Exclusion criteria
Exclusion criteria: 1.Male 2.Locally advanced breast cancer (T4 or Any N2, N3), or distant metastasis 3.Multicentric breast cancer (Note: Multifocal breast cancer, located in one quadrant /area 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 randomization. 9.Patients treated within the last 7 days prior to randomization with: Food or drugs that are known strong and moderate CYP3A4 inhibitors Drugs that are known strong and moderate CYP3A4 inducers 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 including 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 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 abnormality that would impart, in the judgment of the investigator, excess risk associated 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 members or patients who are the sponsor employees directly involved in the conduct 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PEPI EndoPredicTM EPclin Score | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinical Response Rate (CRR) Drop in Ki67 <= 2.7% Rate of pathological CR (pCR) Breast conserving rate (BCR) Type, incidence, severity, seriousness and relationship to study medications of adverse events (AE) and any laboratory abnormalities. Biomarker studies in serum, plasma, urine and tumor tissue | — |
Countries
Australia, Hong Kong S.A.R., China, Japan, South Korea, Taiwan
Contacts
Public ContactElham Fakhrejahani
Kyoto Breast Cancer Research Network
Outcome results
None listed