Clinical trial NCT03609047: Adjuvant Palbociclib in Elderly Patients With Breast Cancer
Official title: A Phase II Study of Adjuvant PALbociclib as an Alternative to CHemotherapy in Elderly patientS With High-risk ER+/HER2- Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer Stage II
Breast Cancer Stage III
Keywords: Breast cancer
elderly patients
CDK4/6 inhibitor
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Pfizer
name: Swedish Association of Breast Oncologists
name: ETOP IBCSG Partners Foundation
name: German Adjuvant Breast Cancer Group
name: SOLTI Breast Cancer Research Group
name: UNICANCER
name: Gruppo Oncologico Italiano di Ricerca Clinica
name: Breast International Group
First posted: 2018-08-01
Enrollment: 366
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized 2:1
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: distant recurrence-free interval (D-RFI) rate
timeFrame: 5 years after first patient inclusion
Secondary outcomes:
measure: Breast cancer specific survival
timeFrame: 5 years after first patient inclusion
measure: Overall survival
timeFrame: 5 years after first patient inclusion
measure: Incidence of permanent treatment discontinuation
timeFrame: 5 years after first patient inclusion
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Brussels
country: Belgium
facility: Institut Jules Bordet-Hopital Universitaire ULB
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Leuven
country: Belgium
facility: U.Z. Leuven - Campus Gasthuisberg
city: Lier
country: Belgium
facility: Heilig Hartziekenhuis Lier
city: Liège
country: Belgium
facility: C.H.U. Sart-Tilman
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas - Campus SL
city: Turnhout
country: Belgium
facility: AZ Turnhout - Campus Sint Elisabeth
city: Bordeaux
country: France
facility: Institut Bergonie
city: Brou
country: France
facility: CHU-Lyon - Hopital Femme Mere Enfant
city: Caen
country: France
facility: Centre Francois Baclesse (CLCC)
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Departemental Vendée
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: CHU de Limoges - Hopital Dupuytren
city: Lyon
country: France
facility: Centre Leon Berard
city: Lyon
country: France
facility: CHU de Lyon - Hopital De La Croix Rousse
city: Nantes
country: France
facility: Hospital prive du Confluent - Centre Catherine de Sienne
city: Pierre-Bénite
country: France
facility: CHU de Lyon - Hopital Lyon Sud
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Cloud
country: France
facility: Institut Curie - l' Hopital de St Cloud
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Essen
country: Germany
facility: Kliniken Essen-Mitte
city: Frankfurt Am Main
country: Germany
facility: Klinikum Frankfurt Hoechst GmbH
city: Homburg / Saar
country: Germany
facility: Universitaetskliniken Des Saarlandes
city: Offenburg
country: Germany
facility: ORTENAU KLINIKUM Offenburg-Gengenbach - Klinikum Offenburg Ebertplatz
city: Ravensburg
country: Germany
facility: Onkologie Haematologie Gemeinschaftspraxis - Studienzentrum Onkologie Ravensburg
city: Schwerte
country: Germany
facility: Marienkrankenhaus Schwerte
city: Stuttgart
country: Germany
facility: Marienhospital Stuttgart
city: Torgau
country: Germany
facility: Kreiskrankenhaus Torgau
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum
city: Witten
country: Germany
facility: Marienhospital Witten
city: Biella
country: Italy
facility: Ospedale Degli Infermi
city: Bolzano
country: Italy
facility: Ospedale Generale Regionale
city: Carpi
country: Italy
facility: Ospedale B. Ramazzini
city: Cattolica
country: Italy
facility: Riccione Hospital Unit - Ospedale Cervesi di Cattolica
city: Faenza
country: Italy
facility: Faenza Hospital Unit - Ospedale degli Infermi
city: Genova
country: Italy
facility: IRCCS Azienda Ospedaliera Universitaria San Martino "IST" - IRCCS - AUO San Martino - IST
city: Guastalla
country: Italy
facility: Ospedale Civile Guastalla
city: Legnago
country: Italy
facility: AULSS 9 - Azienda Unita Locale Socio-Sanitaria N. 9-Mater Salutis Hospital
city: Lugo
country: Italy
facility: Lugo Hospital Unit -Ospedale Umberto I
city: Modena
country: Italy
facility: Azienda Ospedaliero - Universitaria Policlinico di Modena
city: Monza
country: Italy
facility: Ospedale San Gerardo
city: Novafeltria
country: Italy
facility: Rimini Hospital Unit - Ospedale Sacra Famiglia
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena S.P.A.
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Rimini
country: Italy
facility: AUSL Romagna - Rimini Hospital Unit - Infermi Hospital
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta della Salute e della Scienza di Torino - Azienda Ospedaliera Città della Salute e della Scienza di Torino - Ospedale Sant'Anna
city: Torrette
country: Italy
facility: Azienda Ospedaliero Universitaria - Ospedali Riuniti
city: Amman
country: Jordan
facility: King Hussein Cancer Center
city: Gdansk
country: Poland
facility: Medical University Of Gdansk
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Centre - Maria Sklodowska - Curie's National Institute of Oncology - National Research Institute
city: Lisboa
country: Portugal
facility: Champalimaud Clinical Center
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto-- Hospital de Santo Antonio
city: Porto
country: Portugal
facility: Instituto Portugues De Oncologia - Instituto Portugues de Oncologia do Porto
city: Barcelona
country: Spain
facility: Hospital Clinic Universitari de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia - ICO Badalona - Hospital De Mataro
city: Lleida
country: Spain
facility: Hospital Universitari Arnau De Vilanova
city: Madrid
country: Spain
facility: Centro Oncológico MD Anderson
city: Madrid
country: Spain
facility: Hospital Severo Ochoa
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
city: Madrid
country: Spain
facility: Hospital Universitario QuironSalud
city: Madrid
country: Spain
facility: Hospitales HM Sanchinarro-CIOCC
city: Reus
country: Spain
facility: Hospital Sant Joan de Reus
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme
city: Sevilla
country: Spain
facility: Virgen del Rocio University Hospital
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano De Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario De Valencia
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals NHS Foundation Trust - Blackpool Victoria Hospital-NHS Fundation Trust
city: Edinburgh
country: United Kingdom
facility: NHS Lothian - Western General Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust - St. Bartholomew'S Hospital
city: Melrose
country: United Kingdom
facility: NHS Borders - Borders General Hospital Melrose By-pass
Study officials:
affiliation: KU Leuven
name: Hans Wildiers, MD, PhD
role: STUDY_CHAIR
References: