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 (PENELOPE-B trial). - PENELOPE-B

GBG Forschungs GmbH0 sites1,250 target enrollmentMay 22, 2013

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: About one-third of patient with hormone-receptor positive, HER2 negative breast cancer and residual disease after standard of care - including adequate surgery - have a substantial risk of relapse despite the use of adjuvant endocrine therapy.
Sponsor: GBG Forschungs GmbH
Enrollment: 1250
Status: Active, not recruiting
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

May 22, 2013

End Date

TBD

Last Updated

5 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

Female

Investigators

Sponsor

GBG Forschungs GmbH

Eligibility 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 centralised 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 status (IHC score 0\-1 or FISH negative: in\-situ hybridization \[ISH] ratio \< 2\.0\) 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 lymph node can be assessed. In case of bilateral breast cancer hormone\-receptor 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 6 cycles at a minimum duration of 16 weeks. This period must include 6 weeks of a taxane\-containing therapy (exception: 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 randomisation.
•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.

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 randomisation including: Hemoglobin \< 10g/dL (100g/L); ANC \< 2,000/mm³ (\< 2\.0 x 109/L); Platelets \< 100,000/mm³ (\< 100 x 109/L); AST and/or ALT \> 1\.5x upper normal limits (ULN); Alkaline phosphatase \> 2\.5x ULN; Total serum bilirubin \> 1\.25x ULN; Serum creatinine \> 1\.25x ULN or estimated creatinine clearance \< 60mL/min as calculated using the method standard for the institution; severe and relevant co\-morbidity that would interact with the participation in the study.
•3\. Evidence for infection including wound infections, HIV, hepatitis.
•4\. QTc \> 480msec.
•5\. Uncontrolled electrolyte disorders (e.g., hypocalcemia, hypokalemia, hypomagnesemia).
•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 melittus) 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.