None listed
Conditions
Interventions
Drug : Patients will be randomized in a 1:1 ratio to:
• 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 followed by 7 days off treatment in a 28-day cycle for thirteen cycles.
Randomization will be stratified using block randomization by:
• his
Sponsors
GBG Forschungs GmbH
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements. 2. Willingness and ability to provide archived formalin fixed paraffin embedded tissue block or a partial block from surgery after neoadjuvant chemotherapy and from core-biopsy before start of neoadjuvant chemotherapy, which will be used for centralized retrospective confirmation of hormone- and HER2-status and to evaluate correlation between genes, proteins, and mRNAs relevant to the endocrine and cell cycle pathways and sensitivity/resistance to the investigational agents. In case of bilateral breast cancer, tumor tissue of both sides needs to be assessable. 3. Histologically confirmed unilateral or bilateral primary invasive carcinoma of the breast. 4. Residual invasive disease post-neoadjuvant either in the breast or as residual nodal invasion. 5. Centrally confirmed hormone-receptor-positive (=1% ER and/or PR positive stained cells) and HER2-normal (IHC score 0-1 or FISH negative (in-situ hybridization (ISH) ratio) <2.0 status) assessed preferably on tissue from post-neoadjuvant residual invasive disease or core biopsy of the breast, or if no other tissue is available the residual tumor of the lymphnode can be assessed. In case of bilateral breast cancer hormonreceptor positivity and HER2-normal status has to be centrally confirmed for both sides. 6. Centrally assessed Ki-67, pRB, and Cyclin D1 status assessed preferably on post-neoadjuvant residual invasive disease of the breast, or if not possible, of residual nodal invasion or core biopsy. In case of bilateral breast cancer, tumor tissue of both sides needs to be assessable. 7. Patients must have received neoadjuvant chemotherapy of at least 16 weeks. This period must include 6 weeks of a taxane -containing neoadjuvant therapy (Exception: For patients with progressive disease that occurred after at least 6 weeks of taxane-containing neoadjuvant treatment, a total treatment period of less than 16 weeks is also eligible). 8. Adequate surgical treatment including resection of all clinically evident disease and ipsilateral axillary lymph node dissection. Histologically complete resection (R0) of the invasive and ductal in situ tumor is required in case of breast conserving surgery as the final treatment. No evidence of gross residual disease (R2) is required after total mastectomy (R1 resection is acceptable). Axillary dissection is not required in patients with a negative sentinel-node biopsy before (pN0, pN+(mic)) or after (ypN0, ypN+(mic) neoadjuvant chemotherapy. 9. Less than 16 weeks interval since the date of final surgery or less than 10 weeks from completing radiotherapy (whichever occurs last) at date of randomization. 10. Completion of adjuvant radiotherapy according to standard guidelines (e.g. AGO Mamma, NCCN) is strongly recommended. If radiotherapy is not performed the reason for this needs to be documented in the eCRF. 11. No clinical evidence for locoregional or distant relapse during or after preoperative chemotherapy. Local progression during chemotherapy is not an exclusion criterion. 12. A clinical-pathologic stage – estrogen/grade (CPS-EG) score of =3, or score 2 if nodal status at surgery is ypN+, calculated using local estrogen receptor status and grade assessed on either core biopsies taken before start of
Exclusion criteria
Exclusion criteria: 1. Known severe hypersensitivity reactions to compounds similar to palbociclib or palbociclib/placebo excipients or to endocrine treatments. 2. Inadequate organ function immediate prior to randomization including: Hemoglobin 1.5 x upper limit of normal (ULN); alkaline phosphatase > 2.5 x ULN, total serum bilirubin > 1.25 x ULN; serum creatinine >1.25 x ULN or estimated creatinine clearance 480 msec 5. Uncontrolled electrolyte disorders (eg, hypocalcemia, hypokalemia, hypo¬magnesemia). 6. Any of the following within 6 months of randomization: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 4.0 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. 7. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any upper gastrointestinal surgery including gastric resection. 8. Prior malignancy (including invasive or ductal in-situ breast cancer) within 5 years prior to randomization, except curatively treated basal cell carcinoma of the skin and carcinoma in situ of the cervix. 9. Current severe acute or uncontrolled chronic systemic disease (e.g. diabetes mellitus) or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. 10. Recent (within the past year) or active suicidal behavior. 11. Pregnancy or lactation period. Women of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment and for 90 days after discontinuation. A serum pregnancy test must be negative in premenopausal women or women with amenorrhea of less than 12 months. 12. Major surgery within 2 weeks prior to randomization. 13. 10 weeks or more have passed since completion of radiotherapy at day of randomization and 16 weeks interval since the date of final surgery have passed. 14. Prior treatment with any CDK4/6 inhibitor. 15. Patients treated within the last 7 days prior to randomization and/or concurrent use of drugs known to be strong CYP3A4 inhibitors or inducers (see appendix 21.3) 16. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to randomization. 17. Male patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| invasive disease free survival (iDFS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Invasive disease-free survival (iDFS) excluding second non-breast cancers;overall survival (OS);distant disease free survival (DDFS);locoregional recurrences-free (LRRFS) survival;iDFS per treatment group in patients with luminal-B tumors (as determined by e.g. PAM50 or any other commercially available test at the time of analysis);compliance and safety according to NCI-CTCAE Version 4.0;patients reported outcomes;health economic outcomes;correlations between exposure and efficacy and/or safety findings | — |
Countries
Korea, Republic of
Contacts
Public ContactYoungLan Hong
Asan Medical Center
Outcome results
None listed