Adjuvant Palbociclib in Elderly Patients With Breast Cancer

NCT03609047 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: EORTC 1745-ETF-BCG
• Study Type: interventional
• Target: 366
• Locations: 9 countries
• Sites: 73

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.

Conditions

Breast Cancer Stage II; Breast Cancer Stage III

Keywords

Breast cancer; elderly patients; CDK4/6 inhibitor

Outcome Measures

Primary Outcomes (1)

• distant recurrence-free interval (D-RFI) rate

  5 years after first patient inclusion

Secondary Outcomes (3)

• 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

Study Arms (2)

experimental palbociclib arm

EXPERIMENTAL

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.

Drug: Palbociclib

control chemotherapy arm

ACTIVE COMPARATOR

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.

Drug: Docetaxel / cyclophosphamide; Drug: doxorubicin/cyclophosphamide; Drug: epirubicin/cyclophosphamide; Drug: paclitaxel

Interventions

Palbociclib DRUG

CDK4/6 inhibitor

experimental palbociclib arm

Docetaxel / cyclophosphamide DRUG

Adjuvant Chemotherapy

control chemotherapy arm

doxorubicin/cyclophosphamide DRUG

Adjuvant Chemotherapy

control chemotherapy arm

epirubicin/cyclophosphamide DRUG

Adjuvant Chemotherapy

control chemotherapy arm

paclitaxel DRUG

Adjuvant Chemotherapy

control chemotherapy arm

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.
• Hemoglobin ≥ 9 g/dL

You may not qualify if:

• 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.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Pfizer: collaborator
• Swedish Association of Breast Oncologists: collaborator
• ETOP IBCSG Partners Foundation: collaborator
• German Adjuvant Breast Cancer Group: collaborator
• SOLTI Breast Cancer Research Group: collaborator
• UNICANCER: collaborator
• Gruppo Oncologico Italiano di Ricerca Clinica: collaborator
• Breast International Group: collaborator

Study Sites (73)

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Institut Jules Bordet-Hopital Universitaire ULB

Brussels, Belgium

Location

AZ Maria Middelares

Ghent, Belgium

Location

U.Z. Leuven - Campus Gasthuisberg

Leuven, Belgium

Location

Heilig Hartziekenhuis Lier

Lier, Belgium

Location

C.H.U. Sart-Tilman

Liège, Belgium

Location

AZ Nikolaas - Campus SL

Sint-Niklaas, Belgium

Location

AZ Turnhout - Campus Sint Elisabeth

Turnhout, Belgium

Location

Institut Bergonie

Bordeaux, France

Location

CHU-Lyon - Hopital Femme Mere Enfant

Brou, France

Location

Centre Francois Baclesse (CLCC)

Caen, France

Location

Centre Jean Perrin

Clermont-Ferrand, France

Location

Centre Hospitalier Departemental Vendée

La Roche-sur-Yon, France

Location

Centre Oscar Lambret

Lille, France

Location

CHU de Limoges - Hopital Dupuytren

Limoges, France

Location

Centre Leon Berard

Lyon, France

Location

CHU de Lyon - Hopital De La Croix Rousse

Lyon, France

Location

Hospital prive du Confluent - Centre Catherine de Sienne

Nantes, France

Location

CHU de Lyon - Hopital Lyon Sud

Pierre-Bénite, France

Location

Centre Henri Becquerel

Rouen, France

Location

Institut Curie - l' Hopital de St Cloud

Saint-Cloud, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Kliniken Essen-Mitte

Essen, Germany

Location

Klinikum Frankfurt Hoechst GmbH

Frankfurt am Main, Germany

Location

Universitaetskliniken Des Saarlandes

Homburg / Saar, Germany

Location

ORTENAU KLINIKUM Offenburg-Gengenbach - Klinikum Offenburg Ebertplatz

Offenburg, Germany

Location

Onkologie Haematologie Gemeinschaftspraxis - Studienzentrum Onkologie Ravensburg

Ravensburg, Germany

Location

Marienkrankenhaus Schwerte

Schwerte, Germany

Location

Marienhospital Stuttgart

Stuttgart, Germany

Location

Kreiskrankenhaus Torgau

Torgau, Germany

Location

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, Germany

Location

Marienhospital Witten

Witten, Germany

Location

Ospedale Degli Infermi

Biella, Italy

Location

Ospedale Generale Regionale

Bolzano, Italy

Location

Ospedale B. Ramazzini

Carpi, Italy

Location

Riccione Hospital Unit - Ospedale Cervesi di Cattolica

Cattolica, Italy

Location

Faenza Hospital Unit - Ospedale degli Infermi

Faenza, Italy

Location

IRCCS Azienda Ospedaliera Universitaria San Martino "IST" - IRCCS - AUO San Martino - IST

Genova, Italy

Location

Ospedale Civile Guastalla

Guastalla, Italy

Location

AULSS 9 - Azienda Unita Locale Socio-Sanitaria N. 9-Mater Salutis Hospital

Legnago, Italy

Location

Lugo Hospital Unit -Ospedale Umberto I

Lugo, Italy

Location

Azienda Ospedaliero - Universitaria Policlinico di Modena

Modena, Italy

Location

Ospedale San Gerardo

Monza, Italy

Location

Rimini Hospital Unit - Ospedale Sacra Famiglia

Novafeltria, Italy

Location

Casa di Cura La Maddalena S.P.A.

Palermo, Italy

Location

Ospedale Santa Maria delle Croci

Ravenna, Italy

Location

AUSL Romagna - Rimini Hospital Unit - Infermi Hospital

Rimini, Italy

Location

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

Location

Azienda Ospedaliero Universitaria - Ospedali Riuniti

Torrette, Italy

Location

King Hussein Cancer Center

Amman, Jordan

Location

Medical University Of Gdansk

Gdansk, Poland

Location

Maria Sklodowska-Curie Memorial Cancer Centre - Maria Sklodowska - Curie's National Institute of Oncology - National Research Institute

Warsaw, Poland

Location

Champalimaud Clinical Center

Lisbon, Portugal

Location

Centro Hospitalar do Porto-- Hospital de Santo Antonio

Porto, Portugal

Location

Instituto Portugues De Oncologia - Instituto Portugues de Oncologia do Porto

Porto, Portugal

Location

Hospital Clinic Universitari de Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Institut Catala d'Oncologia - ICO Badalona - Hospital De Mataro

Barcelona, Spain

Location

Hospital Universitari Arnau De Vilanova

Lleida, Spain

Location

Centro Oncológico MD Anderson

Madrid, Spain

Location

Hospital Severo Ochoa

Madrid, Spain

Location

Hospital Universitario 12 De Octubre

Madrid, Spain

Location

Hospital Universitario QuironSalud

Madrid, Spain

Location

Hospitales HM Sanchinarro-CIOCC

Madrid, Spain

Location

Hospital Sant Joan de Reus

Reus, Spain

Location

Hospital Universitario Virgen de Valme

Seville, Spain

Location

Virgen del Rocio University Hospital

Seville, Spain

Location

Fundacion Instituto Valenciano De Oncologia

Valencia, Spain

Location

Hospital Clinico Universitario De Valencia

Valencia, Spain

Location

Blackpool Teaching Hospitals NHS Foundation Trust - Blackpool Victoria Hospital-NHS Fundation Trust

Blackpool, United Kingdom

Location

NHS Lothian - Western General Hospital

Edinburgh, United Kingdom

Location

Barts Health NHS Trust - St. Bartholomew'S Hospital

London, United Kingdom

Location

NHS Borders - Borders General Hospital Melrose By-pass

Melrose, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; CP protocol; AC protocol; EC regimen; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Hans Wildiers, MD, PhD

  KU Leuven

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Randomized 2:1

Study Record Dates

• First Submitted: June 18, 2018
• First Posted: August 1, 2018
• Study Start: June 14, 2019
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2032
• Last Updated: January 24, 2024

Record last verified: 2024-01

Locations

IT (17); GB (4); JO (1); ES (14); BE (8); FR (14); PT (3); PL (2); DE (10)