residual invasive breast cancer and high CPS-EG score after neoadjuvant chemotherapy receiving standard adjuvant endocrine therapy for HRpositive/HER2-normal primary breast cancer
Conditions
Interventions
Arm A : palbociclib at a dose of 125 mg once daily, day 1 to day 21 followed by 7 days off treatment in a 28-day cycle for thirteen cycles
Arm B : Placebo of palbociclib once daily day 1 to day 21 fol
Sponsors
GBG Forschungs GmbH
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: Histologically confirmed unilateral or bilateral primary invasive carcinoma of the breast. Residual invasive disease post-neoadjuvant either in the breast or as residual nodal invasion. Centrally confirmed hormone-receptor-positive and HER2-normal assessed preferably on tissue from post-neoadjuvant residual invasive disease or core biopsy of the breast (Exception). In case of bilateral breast cancer status has to be confirmed centrally for both sides. Centrally assessed Ki-67, pRB, and Cyclin D1 status assessed preferably on post-neoadjuvant residual invasive disease of the breast (Exception). Neoadjuvant chemotherapy of at least 16 weeks. This period must include 6 weeks of a taxane -containing neoadjuvant therapy (Exception) Adequate surgical treatment (Specifics). R0 required in case of breast conserving surgery as the final treatment. Less than 16 weeks interval since the date of final surgery or less than 10 weeks from completing radiotherapy (whichever occurs last) and date of randomization Completion of adjuvant radiotherapy. (Radiotherapy indications) No clinical evidence for locoregional or distant relapse during or after preoperative chemotherapy. (Exception) CPS-EG score of >=3 or score 2 if nodal status at surgery is patient is ypN+,assessed on either core biopsies taken before start of neoadjuvant treatment or surgical specimen. Age at diagnosis >= 18 years. ECOG PS 0 or 1. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE ver. 4.0 Grade <=1 (Exception). Estimated life expectancy >= 5 years irrespective of the diagnosis of breast cancer. The patient must be accessible for scheduled visits, treatment and follow-up.
Exclusion criteria
Exclusion criteria: Severe hypersensitivity reactions to compounds similar to palbociclib or palbociclib/placebo excipients or to endocrine treatments. Hemoglobin <10g/dL (100g/L) ANC < 2000/mm&sup3; (< 2.0 x 109/L); Platelets <100,000/mm&sup3; (< 100 x 109/L); AST and/or ALT >1.5 x upper normal limits (ULN); alkaline phosphatase > 2.5 x ULN, total serum bilirubin > 1.25 x ULN; serum creatinine >1.25 x ULN or estimated creatinine clearance < 60 mL/min; severe and relevant co-morbidity that would interact with the participation in the study Evidence for infection. QTc >480 msec or a family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes. Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug. Abnormal cardiac functions within 6 months of randomization (Definition) Active gastrointestinal abnormalities (Definition), or any upper gastrointestinal surgery. Prior malignancy within 5 years prior to randomization (Exception). Any abnormalities in the judgment of the investigator, which would make the patient inappropriate for entry into this study. Recent (within the past year) or active suicidal behavior. Pregnancy or lactation period. Major surgery within 2 weeks prior to randomization. Prior endocrine treatment in addition to the neoadjuvant chemotherapy is acceptable. Prior treatment with any CDK4/6 inhibitor. Patients treated within the last 7 days prior to randomization with and/or still using strong CYP3A4 inhibitors / inducers, or QT interval prolonging drugs. Using other experimental drugs. Participating in another clinical trial with any investigational unmarketed drug within 30 days prior to study entry. Male patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Invasive Disease-free survival | — |
Countries
Japan,Asia(except Japan),North America,South America,Australia,Europe
Contacts
Public ContactJun Fukase
JBCRG(Japan Breast Cancer Research Group) Head Office
Outcome results
None listed