A Study of Palbociclib in Addition to Standard Endocrine Treatment in Hormone Receptor Positive Her2 Normal Patients With Residual Disease After Neoadjuvant Chemotherapy and Surgery (PENELOPE-B)
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|ClinicalTrials.gov Identifier: NCT01864746|
Recruitment Status : Active, not recruiting
First Posted : May 30, 2013
Last Update Posted : April 12, 2022
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Hormonreceptor Positive Her2-normal Postneoadjuvant Treatment With CDK 4/6 Inhibitor CPS-EG Score||Drug: Palbociclib PD-0332991 Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1250 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||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"|
|Study Start Date :||November 2013|
|Actual Primary Completion Date :||October 2020|
|Estimated Study Completion Date :||November 2023|
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
Drug: Palbociclib PD-0332991
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
Other Name: Ibrance
Placebo Comparator: Placebo
Placebo of palbociclib once daily day 1 to day 21 followed by 7 days off treatment in a28-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
- Invasive disease free survival (iDFS) for palbociclib vs. placebo in patients with high CPS-EG score after neoadjuvant chemotherapy receiving standard adjuvant endocrine therapy for HR-positive/HER2-normal primary breast cancer. [ Time Frame: Time-to-Event Outcome measure. Final analysis on the primary endpoint and secondary efficacy endpoints (except for OS) Analysis will be conducted when 255 events observed. Assessed until approx. Dec 2020. ]
Invasive disease-free survival (iDFS) is defined according to Hudis (J Clin Oncol 2007) as the time period between randomization and first event (ipsi- or contralateral invasive in-breast or loco-regional recurrence, distant recurrence, death from breast cancer, death from non-breast cancer cause, death from unknown cause, invasive contralateral breast cancer, second primary invasive cancer (non-breast)).
Two interim efficacy analyses will be performed in the study. First interim analysis: Safety, early stopping Second interim analysis: Safety, early stopping, sample size adjustment
- iDFS excluding second non-breast cancers [ Time Frame: Time-to-Event Outcome Measure up to 71 months ]Invasive disease-free survival (iDFS) is defined according to Hudis (J Clin Oncol 2007) as the time period between randomization and first event.
- distant disease free survival (DDFS) [ Time Frame: Time-to-Event Outcome Measure up to 71 months ]Distant disease free survival (DDFS) is defined as the time period between randomization and diagnosis of first distant breast cancer recurrences.
- overall survival (OS) [ Time Frame: Time-to-Event Outcome Measure up to 71 months - and post study ]Overall survival (OS) is defined as the time period between randomization and death of any cause. An interim OS analysis will be conducted at the time of final iDFS analysis and final OS analysis will be conducted at a later time. In addition Relapse and Mortality data will be collected post study.
- 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) [ Time Frame: Time-to-Event Outcome Measure up to 71 months ]see above for event definition
- compliance and safety according to NCI-CTCAE Version 4.0 [ Time Frame: 2019 and with interim analysis on safety ]Descriptive statistics for the 2 treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.
- patients reported outcomes EORTC QLQ C30, • EORTC QLQ BR-23, • EORTC QLQ FA-13 Fatigue, • GAD7 patient self-rating mood scale [ Time Frame: Change Outcome up to 71 months ]Screening, Cycle 1, 3, 5, 7, 9, 11, End of treatment and thereafter every 6 months until 233 events are observed
- quality-adjusted life years (QALY), health economic outcomes EQ-5D [ Time Frame: Change Outcome Measure up to 71 months ]Screening, Cycle 1, 3, 5, 7, 9, 11, End of treatment and thereafter every 6 months
- Area under the Curve (AUC), Cmax [ Time Frame: pre-dose, 2, 4, 6, 8, and 24 hours ]
Drug-drug interactions (DDI) potential for palbociclib - endocrine combination therapy
In the first 24 patients receiving tamoxifen or anastrozol together with palbociclib/placebo plasma PK samples will be drawn on pre-dose and 2, 4, 6, 8, and 24 hours post-dose for DDI assessment.
In the first 24 patients receiving gosereline and tamoxifen together with palbociclib/placebo, plasma PK samples will be drawn on Cycle 2 and Cycle 3 Days 1 and Day 14 pre-dose for DDI assessment.
In addition in the first 24 patients receiving gosereline and tamoxifen together with palbociclib/placebo, plasma PK samples will be drawn on Cycle 2 and Cycle 3 Days 1 and Day 14 pre-dose for DDI assessment.
- correlations between exposure and efficacy and/or safety findings [ Time Frame: Pharmacokinetic Outcomes Measure mit Cmax and AUC ]Trough concentrations of PD-0332991 will be collected pre-dose on Day 14 of cycle 1 and 2 for all patients (including letrozol taking patients).
- Scores and markers for their prognostic value in this specific trial setting and their predictive information on the efficacy and/or safety of palbociclib [ Time Frame: pre and posttherapy up to 13months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01864746
|United States, Pennsylvania|
|Pittsburgh, Pennsylvania, United States, 15212|
|Australia, New South Wales|
|Contact: Australia and New Zealand Breast Cancer Trials Group|
|Newcastle, New South Wales, Australia, PO Box 155|
|Contact: Austrian Breast & Colorectal Cancer Study Group|
|Vienna, Austria, 1090|
|Contact: NSABP Foundation|
|Multiple Locations, Canada|
|Paris, France, 75654|
|Contact: German Breast Group|
|Neu-Isenburg, Germany, 63263|
|Contact: Cancer Trials Ireland|
|Dublin, Ireland, 2|
|Contact: Japan Breast Cancer Research Group|
|Tokyo, Japan, 103-0016|
|Korea, Republic of|
|Contact: Korea Cancer Study Group|
|Seoul, Korea, Republic of, 138-736|
|San Sebastián de los Reyes, Spain, 28703|
|Contact: Institute of Cancer Research|
|London, United Kingdom, SW7 3RP|
|Principal Investigator:||Sibylle Loibl, MD, Prof||ASCO, ESMO, EORTC-TRAFO, ESGO, DKG, AGO|