Adjuvant Palbociclib in Elderly Patients With Breast Cancer

NCT ID: NCT03609047

Last Updated: 2024-01-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 366 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-14
• Study Completion Date: 2032-09-30

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.

Conditions

Breast Cancer Stage II; Breast Cancer Stage III

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

experimental palbociclib arm

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.

Group Type: EXPERIMENTAL

Palbociclib

Intervention Type: DRUG

CDK4/6 inhibitor

control chemotherapy arm

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.

Group Type: ACTIVE_COMPARATOR

Docetaxel / cyclophosphamide

Intervention Type: DRUG

Adjuvant Chemotherapy

doxorubicin/cyclophosphamide

Intervention Type: DRUG

Adjuvant Chemotherapy

epirubicin/cyclophosphamide

Intervention Type: DRUG

Adjuvant Chemotherapy

paclitaxel

Intervention Type: DRUG

Adjuvant Chemotherapy

Interventions

Palbociclib

CDK4/6 inhibitor

Intervention Type: DRUG

Docetaxel / cyclophosphamide

Adjuvant Chemotherapy

Intervention Type: DRUG

doxorubicin/cyclophosphamide

Adjuvant Chemotherapy

Intervention Type: DRUG

epirubicin/cyclophosphamide

Adjuvant Chemotherapy

Intervention Type: DRUG

paclitaxel

Adjuvant Chemotherapy

Intervention Type: DRUG

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.

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Swedish Association of Breast Oncologists

UNKNOWN

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: collaborator

German Adjuvant Breast Cancer Group

OTHER

Sponsor Role: collaborator

SOLTI Breast Cancer Research Group

OTHER

Sponsor Role: collaborator

UNICANCER

OTHER

Sponsor Role: collaborator

Gruppo Oncologico Italiano di Ricerca Clinica

OTHER

Sponsor Role: collaborator

Breast International Group

OTHER

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hans Wildiers, MD, PhD

Role: STUDY_CHAIR

KU Leuven

Locations

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Institut Jules Bordet-Hopital Universitaire ULB

Brussels, , Belgium

AZ Maria Middelares

Ghent, , Belgium

U.Z. Leuven - Campus Gasthuisberg

Leuven, , Belgium

Heilig Hartziekenhuis Lier

Lier, , Belgium

C.H.U. Sart-Tilman

Liège, , Belgium

AZ Nikolaas - Campus SL

Sint-Niklaas, , Belgium

AZ Turnhout - Campus Sint Elisabeth

Turnhout, , Belgium

Institut Bergonie

Bordeaux, , France

CHU-Lyon - Hopital Femme Mere Enfant

Brou, , France

Centre Francois Baclesse (CLCC)

Caen, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Centre Hospitalier Departemental Vendée

La Roche-sur-Yon, , France

Centre Oscar Lambret

Lille, , France

CHU de Limoges - Hopital Dupuytren

Limoges, , France

Centre Leon Berard

Lyon, , France

CHU de Lyon - Hopital De La Croix Rousse

Lyon, , France

Hospital prive du Confluent - Centre Catherine de Sienne

Nantes, , France

CHU de Lyon - Hopital Lyon Sud

Pierre-Bénite, , France

Centre Henri Becquerel

Rouen, , France

Institut Curie - l' Hopital de St Cloud

Saint-Cloud, , France

Institut Claudius Regaud

Toulouse, , France

Kliniken Essen-Mitte

Essen, , Germany

Klinikum Frankfurt Hoechst GmbH

Frankfurt am Main, , Germany

Universitaetskliniken Des Saarlandes

Homburg / Saar, , Germany

ORTENAU KLINIKUM Offenburg-Gengenbach - Klinikum Offenburg Ebertplatz

Offenburg, , Germany

Onkologie Haematologie Gemeinschaftspraxis - Studienzentrum Onkologie Ravensburg

Ravensburg, , Germany

Marienkrankenhaus Schwerte

Schwerte, , Germany

Marienhospital Stuttgart

Stuttgart, , Germany

Kreiskrankenhaus Torgau

Torgau, , Germany

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, , Germany

Marienhospital Witten

Witten, , Germany

Ospedale Degli Infermi

Biella, , Italy

Ospedale Generale Regionale

Bolzano, , Italy

Ospedale B. Ramazzini

Carpi, , Italy

Riccione Hospital Unit - Ospedale Cervesi di Cattolica

Cattolica, , 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

Lugo Hospital Unit -Ospedale Umberto I

Lugo, , Italy

Azienda Ospedaliero - Universitaria Policlinico di Modena

Modena, , Italy

Ospedale San Gerardo

Monza, , Italy

Rimini Hospital Unit - Ospedale Sacra Famiglia

Novafeltria, , 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

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

Azienda Ospedaliero Universitaria - Ospedali Riuniti

Torrette, , Italy

King Hussein Cancer Center

Amman, , Jordan

Medical University Of Gdansk

Gdansk, , Poland

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

Warsaw, , Poland

Champalimaud Clinical Center

Lisbon, , Portugal

Centro Hospitalar do Porto-- Hospital de Santo Antonio

Porto, , Portugal

Instituto Portugues De Oncologia - Instituto Portugues de Oncologia do Porto

Porto, , Portugal

Hospital Clinic Universitari de Barcelona

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

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 Severo Ochoa

Madrid, , Spain

Hospital Universitario 12 De Octubre

Madrid, , Spain

Hospital Universitario QuironSalud

Madrid, , Spain

Hospitales HM Sanchinarro-CIOCC

Madrid, , Spain

Hospital Sant Joan de Reus

Reus, , Spain

Hospital Universitario Virgen de Valme

Seville, , Spain

Virgen del Rocio University Hospital

Seville, , Spain

Fundacion Instituto Valenciano De Oncologia

Valencia, , Spain

Hospital Clinico Universitario De Valencia

Valencia, , Spain

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

Blackpool, , United Kingdom

NHS Lothian - Western General Hospital

Edinburgh, , United Kingdom

Barts Health NHS Trust - St. Bartholomew'S Hospital

London, , United Kingdom

NHS Borders - Borders General Hospital Melrose By-pass

Melrose, , United Kingdom

Countries

Belgium; France; Germany; Italy; Jordan; Poland; Portugal; Spain; United Kingdom

Other Identifiers

EORTC 1745-ETF-BCG

Identifier Type: -

Identifier Source: org_study_id