Adjuvant Palbociclib in Elderly Patients With Breast Cancer
- Conditions
- Breast Cancer Stage IIBreast Cancer Stage III
- Interventions
- Drug: doxorubicin/cyclophosphamideDrug: epirubicin/cyclophosphamide
- Registration Number
- NCT03609047
- Brief Summary
Phase II study to assess the efficacy of the combination of at least 5 year endocrine therapy and 2 year-palbociclib as adjuvant systemic treatment instead of adjuvant chemotherapy followed by endocrine therapy in older patients with stage II-III ER+/HER2- early breast cancer.
- Detailed Description
The primary objective of this trial is to assess the efficacy of the combination of at least 5 year endocrine therapy and 2 year-palbociclib as adjuvant systemic treatment instead of adjuvant chemotherapy followed by endocrine therapy in older patients with stage II-III ER+/HER2- early breast cancer.
This is a two-arm open-label multi-center randomized (2:1) non-comparative phase II study in elderly patients with stage II/III, ER+, HER2- early breast cancer for whom treatment with chemotherapy is indicated.
Patients will be randomized with a 2:1 allocation rate to the following treatment arm:
* experimental palbociclib arm: Standard adjuvant endocrine therapy for a duration of at least 5 years + palbociclib for a total duration of up to 2 years.
* control chemotherapy arm: adjuvant chemotherapy (4 cycles of docetaxel/doxorubicin/epirubicin-cyclophosphamide; or of weekly paclitaxel D1, D8, and D15 q3w if a 3 weekly schedule is not desired), followed by standard adjuvant endocrine therapy for a duration of at least 5 years.
The primary endpoint of the study is the 3-year D-RFI rate in the experimental arm.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 366
- Women or men with stage II or stage III, early invasive breast cancer according to the UICC 8th edition for TNM classification
- Histologically confirmed Estrogen Receptor ER+ (at least 10 % of cells staining positive for ER), Human Epidermal Growth Factor Receptor 2 (HER-2) negative, early invasive breast cancer based on results of local pathology. Testing may be performed on diagnostic core biopsy or resection specimen.
- In patients with multicentric, multifocal and/or bilateral breast cancer, all histopathologically examined invasive tumors must meet pathologic criteria regarding ER and HER2-status described above.
- Adjuvant chemotherapy indicated and feasible according to treating physician and patient, based on standard clinicopathological parameters (tumor size, lymph node involvement, general health status, proliferation marker, patient wish) and gene expression profile if available.
- Adjuvant chemotherapy combining both anthracycline and taxanes considered not indicated or not feasible according to treating physician.
- No evidence of macroscopic distant metastases, investigated according to local institutional guidelines.
- Age ≥70 years
- Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
- Patient must have undergone breast +/- axillary surgery with curative intent for the current malignancy ≤8 weeks before randomization.
- The maximum duration from last surgery to the start of the first adjuvant treatment is 9 weeks.
- Patients must have sufficient resolution of any surgical side effects from the last surgery per physician assessment, with no active wound healing complications at the time of randomization.
- Incentive to undergo adjuvant radiation therapy when indicated per local institutional guidelines.
- Note: For patients in the palbociclib arm, radiation therapy when indicated has to start ≤9 weeks after last surgery. The endocrine therapy can be initiated during or after the radiation therapy but not later than 3 weeks after the last radiotherapy. Palbociclib has to start ≤3 weeks after the last radiotherapy. When radiation therapy is not indicated, endocrine therapy and palbociclib have to be initiated ≤9 weeks after last surgery.
- Note: For patients in the chemotherapy arm, chemotherapy has to be the first adjuvant treatment and has to start ≤9 weeks after the last surgery. When radiation therapy is indicated, this treatment has to start ≤6 weeks after the last chemotherapy administration. Adjuvant endocrine therapy can be initiated during or after the radiation therapy but not later than 3 weeks after the last radiotherapy. When radiation therapy is not indicated, endocrine therapy has to be initiated ≤6 weeks after last chemotherapy administration.
- Adequate organ function, evidenced by the following laboratory results within 3 weeks prior to inclusion:
- Hemoglobin ≥ 9 g/dL
- Absolute neutrophil count (ANC) ≥ 1500/mm3
- Platelet count ≥ 100,000/mm3
- Total bilirubin ≤ 1.5 upper limit of normal (ULN), or total bilirubin ≤ 3.0 × ULN in patients with documented Gilbert's Syndrome.
- Glomerular Filtration Rate (GFR) ≥ 30 ml/min according to Modification of Diet in Renal Disease (MDRD) formula or Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) formula or Cockcroft and Gault formula
- Serum Glutamic Oxaloacetic Transaminase (Aspartate Transaminase), Serum Glutamic Pyruvic Transaminase (Alanine Transaminase) and alkaline phosphatase ≤ 2.5 × ULN
- Patients must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption.
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- Before patient registration/randomization, written informed consent must be obtained according to ICH/GCP, and national/local regulations.
- Previous history of invasive breast cancer
- Systemic anticancer therapy prior to the breast cancer surgery
- Prior therapy with any Cyclin-Dependent Kinase (CDK)4/6 inhibitor
- Concurrent investigational agent within 28 days of randomization
- Concomitant anticancer treatment with the exception of bone antiresorptive agents or Luteinizing Hormone-Releasing Hormone agonists in male patients treated with an aromatase-inhibitor
- History of allergic reactions attributed to compounds of chemical or biological composition similar to palbociclib or to chemotherapy components
- Medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization (see Chapter 5.6.3 for list of CYP3A inhibitors and inducers)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including known HIV, active hepatitis B and/or hepatitis C infection), symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or uncontrolled diabetes.
- Other malignancy within the last 5 years except: adequately treated non-metastatic non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ of the breast.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description control chemotherapy arm Docetaxel / cyclophosphamide Adjuvant chemotherapy: 4 cycles docetaxel 75 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles doxorubicin 60 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles epirubicin 90 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles weekly paclitaxel 80 mg/m2 D1, D8, and D15 q3w Followed by standard adjuvant endocrine therapy for a duration of at least 5 years. control chemotherapy arm doxorubicin/cyclophosphamide Adjuvant chemotherapy: 4 cycles docetaxel 75 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles doxorubicin 60 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles epirubicin 90 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles weekly paclitaxel 80 mg/m2 D1, D8, and D15 q3w Followed by standard adjuvant endocrine therapy for a duration of at least 5 years. control chemotherapy arm epirubicin/cyclophosphamide Adjuvant chemotherapy: 4 cycles docetaxel 75 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles doxorubicin 60 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles epirubicin 90 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles weekly paclitaxel 80 mg/m2 D1, D8, and D15 q3w Followed by standard adjuvant endocrine therapy for a duration of at least 5 years. control chemotherapy arm paclitaxel Adjuvant chemotherapy: 4 cycles docetaxel 75 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles doxorubicin 60 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles epirubicin 90 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles weekly paclitaxel 80 mg/m2 D1, D8, and D15 q3w Followed by standard adjuvant endocrine therapy for a duration of at least 5 years. experimental palbociclib arm Palbociclib Standard adjuvant endocrine therapy for a duration of at least 5 years + palbociclib (one capsule 125mg QD, orally, for 21 days followed by 7 days off treatment) for a total duration of up to 2 years.
- Primary Outcome Measures
Name Time Method distant recurrence-free interval (D-RFI) rate 5 years after first patient inclusion
- Secondary Outcome Measures
Name Time Method Breast cancer specific survival 5 years after first patient inclusion Overall survival 5 years after first patient inclusion Incidence of permanent treatment discontinuation 5 years after first patient inclusion
Trial Locations
- Locations (73)
Heilig Hartziekenhuis Lier
🇧🇪Lier, Belgium
Medical University Of Gdansk
🇵🇱Gdansk, Poland
Centro Hospitalar do Porto-- Hospital de Santo Antonio
🇵🇹Porto, Portugal
Hospital Severo Ochoa
🇪🇸Madrid, Spain
AZ Maria Middelares
🇧🇪Gent, Belgium
Centre Hospitalier Departemental Vendée
🇫🇷La Roche-sur-Yon, France
Kliniken Essen-Mitte
🇩🇪Essen, Germany
Universitaetskliniken Des Saarlandes
🇩🇪Homburg / Saar, Germany
C.H.U. Sart-Tilman
🇧🇪Liège, Belgium
CHU-Lyon - Hopital Femme Mere Enfant
🇫🇷Brou, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Marienhospital Stuttgart
🇩🇪Stuttgart, Germany
Kreiskrankenhaus Torgau
🇩🇪Torgau, Germany
ORTENAU KLINIKUM Offenburg-Gengenbach - Klinikum Offenburg Ebertplatz
🇩🇪Offenburg, Germany
Marienhospital Witten
🇩🇪Witten, Germany
Riccione Hospital Unit - Ospedale Cervesi di Cattolica
🇮🇹Cattolica, Italy
Azienda Ospedaliero - Universitaria Policlinico di Modena
🇮🇹Modena, Italy
Lugo Hospital Unit -Ospedale Umberto I
🇮🇹Lugo, Italy
Azienda Ospedaliero Universitaria - Ospedali Riuniti
🇮🇹Torrette, Italy
Casa di Cura La Maddalena S.P.A.
🇮🇹Palermo, Italy
Ospedale Santa Maria delle Croci
🇮🇹Ravenna, Italy
AUSL Romagna - Rimini Hospital Unit - Infermi Hospital
🇮🇹Rimini, Italy
Blackpool Teaching Hospitals NHS Foundation Trust - Blackpool Victoria Hospital-NHS Fundation Trust
🇬🇧Blackpool, United Kingdom
NHS Lothian - Western General Hospital
🇬🇧Edinburgh, United Kingdom
Fundacion Instituto Valenciano De Oncologia
🇪🇸Valencia, Spain
Centre Francois Baclesse (CLCC)
🇫🇷Caen, France
Institut Bergonie
🇫🇷Bordeaux, France
CHU de Lyon - Hopital De La Croix Rousse
🇫🇷Lyon, France
Hospital prive du Confluent - Centre Catherine de Sienne
🇫🇷Nantes, France
Centre Henri Becquerel
🇫🇷Rouen, France
Centre Jean Perrin
🇫🇷Clermont Ferrand, France
CHU de Limoges - Hopital Dupuytren
🇫🇷Limoges, France
Centre Oscar Lambret
🇫🇷Lille, France
CHU de Lyon - Hopital Lyon Sud
🇫🇷Pierre-Bénite, France
Klinikum Frankfurt Hoechst GmbH
🇩🇪Frankfurt Am Main, Germany
Centre Leon Berard
🇫🇷Lyon, France
Institut Curie - l' Hopital de St Cloud
🇫🇷Saint-Cloud, France
Schwarzwald-Baar Klinikum
🇩🇪Villingen-Schwenningen, Germany
Onkologie Haematologie Gemeinschaftspraxis - Studienzentrum Onkologie Ravensburg
🇩🇪Ravensburg, Germany
Marienkrankenhaus Schwerte
🇩🇪Schwerte, Germany
Ospedale Degli Infermi
🇮🇹Biella, Italy
Ospedale Generale Regionale
🇮🇹Bolzano, Italy
Ospedale B. Ramazzini
🇮🇹Carpi, Italy
Faenza Hospital Unit - Ospedale degli Infermi
🇮🇹Faenza, Italy
IRCCS Azienda Ospedaliera Universitaria San Martino "IST" - IRCCS - AUO San Martino - IST
🇮🇹Genova, Italy
Ospedale Civile Guastalla
🇮🇹Guastalla, Italy
AULSS 9 - Azienda Unita Locale Socio-Sanitaria N. 9-Mater Salutis Hospital
🇮🇹Legnago, Italy
Rimini Hospital Unit - Ospedale Sacra Famiglia
🇮🇹Novafeltria, Italy
Ospedale San Gerardo
🇮🇹Monza, Italy
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Azienda Ospedaliera Citta della Salute e della Scienza di Torino - Azienda Ospedaliera Città della Salute e della Scienza di Torino - Ospedale Sant'Anna
🇮🇹Torino, Italy
Maria Sklodowska-Curie Memorial Cancer Centre - Maria Sklodowska - Curie's National Institute of Oncology - National Research Institute
🇵🇱Warsaw, Poland
Hospital Clinic Universitari de Barcelona
🇪🇸Barcelona, Spain
Institut Catala d'Oncologia - ICO Badalona - Hospital De Mataro
🇪🇸Barcelona, Spain
Hospital Universitari Arnau De Vilanova
🇪🇸Lleida, Spain
Centro Oncológico MD Anderson
🇪🇸Madrid, Spain
Hospital Universitario 12 De Octubre
🇪🇸Madrid, Spain
Hospital Universitario QuironSalud
🇪🇸Madrid, Spain
Hospitales HM Sanchinarro-CIOCC
🇪🇸Madrid, Spain
Virgen del Rocio University Hospital
🇪🇸Sevilla, Spain
Hospital Sant Joan de Reus
🇪🇸Reus, Spain
Hospital Universitario Virgen de Valme
🇪🇸Sevilla, Spain
Hospital Clinico Universitario De Valencia
🇪🇸Valencia, Spain
Barts Health NHS Trust - St. Bartholomew'S Hospital
🇬🇧London, United Kingdom
NHS Borders - Borders General Hospital Melrose By-pass
🇬🇧Melrose, United Kingdom
AZ Turnhout - Campus Sint Elisabeth
🇧🇪Turnhout, Belgium
King Hussein Cancer Center
🇯🇴Amman, Jordan
AZ Nikolaas - Campus SL
🇧🇪Sint-Niklaas, Belgium
Instituto Portugues De Oncologia - Instituto Portugues de Oncologia do Porto
🇵🇹Porto, Portugal
Institut Jules Bordet-Hopital Universitaire ULB
🇧🇪Brussels, Belgium
U.Z. Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Champalimaud Clinical Center
🇵🇹Lisboa, Portugal