SHS_492291 KAPH CABP 15017
Phase III Study Evaluating Palbociclib (PD-0332991), a Cyclin-Dependent Kinase (CDK) 4/6 Inhibitor in Patients With Hormone-receptor-positive, HER2-normal Primary Breast Cancer With High Relapse Risk after Neoadjuvant Chemotherapy: PENELOPEB
The PENELOPEB study is designed to demonstrate that in the background of standard anti-hormonal therapy palbociclib provides superior invasive disease-free survival (iDFS) compared to placebo in pre- and postmenopausal women with HR-positive/HER2-normal early breast cancer at high risk of relapse after showing less than pathological complete response to neoadjuvant taxane- containing chemotherapy. Considering the high risk of recurrence in patients after neoadjuvant chemotherapy and a high CPS-EG score, palbociclib appears to be an attractive option with a favourable safety profile for these patients.
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.
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.
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.
Received neoadjuvant chemotherapy of at least 16 weeks.
Adequate surgical treatment including resection of all clinically evident disease and ipsilateral axillary lymph node dissection.
Completion of adjuvant radiotherapy.
No clinical evidence for locoregional or distant relapse during or after preoperative chemotherapy.
A clinical-pathologic stage - estrogen/grade (CPS-EG) score of >=3, or score 2 if nodal status at surgery isypN+.
Age at diagnosis at least 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.0 Grade ≤1, with some exceptions.
Estimated life expectancy of at least 5 years irrespective of the diagnosis of breast cancer.
Known severe hypersensitivity reactions to compounds similar to palbociclib or palbociclib/placebo excipients or to endocrine treatments.
Inadequate organ function immediate prior to randomization.
Evidence of infection including wound infections, HIV, hepatitis.
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 (TdP).
Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug.
Any of the following within 6 months of randomization: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any upper gastrointestinal surgery including gastric resection.
Prior malignancy (including invasive or ductal in-situ breast cancer) within 5 years, except treated basal cell carcinoma of the skin and carcinoma in situ of the cervix.
Current severe acute or uncontrolled chronic systemic disease, psychiatric condition, or laboratory abnormality that may increase the risk of study participation or investigational product administration.
Recent or active suicidal behavior.
Major surgery within 2 weeks prior to randomization.
Prior endocrine treatment in addition to neoadjuvant chemotherapy is acceptable.
Prior treatment with any CDK4/6 inhibitor.
Patients treated within the last 7 days prior to randomization and/or concurrent use of drugs known to be strong CYP3A4 inhibitors or inducers or drugs known to prolong the QT interval.
Henry Kaplan, M.D.
NSABP (National Surgical Adjuvant Breast and Bowel Project)