Adjuvant Palbociclib in Elderly Patients With Breast Cancer

Breast Cancer Stage II Clinical Trial

— Appalaches  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03609047
• Other study ID #: EORTC 1745-ETF-BCG
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 14, 2019
• Est. completion date: September 30, 2032

Study information

• Verified date: January 2024
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 366
• Est. completion date: September 30, 2032
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer Stage II
• Breast Cancer Stage III
• Breast Neoplasms

Intervention

Drug:
• Palbociclib
CDK4/6 inhibitor
• Docetaxel / cyclophosphamide
Adjuvant Chemotherapy
• doxorubicin/cyclophosphamide
Adjuvant Chemotherapy
• epirubicin/cyclophosphamide
Adjuvant Chemotherapy
• paclitaxel
Adjuvant Chemotherapy

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Institut Jules Bordet-Hopital Universitaire ULB	Brussels
Belgium	AZ Maria Middelares	Gent
Belgium	U.Z. Leuven - Campus Gasthuisberg	Leuven
Belgium	C.H.U. Sart-Tilman	Liège
Belgium	Heilig Hartziekenhuis Lier	Lier
Belgium	AZ Nikolaas - Campus SL	Sint-Niklaas
Belgium	AZ Turnhout - Campus Sint Elisabeth	Turnhout
France	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
Germany	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
Italy	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
Jordan	King Hussein Cancer Center	Amman
Poland	Medical University Of Gdansk	Gdansk
Poland	Maria Sklodowska-Curie Memorial Cancer Centre - Maria Sklodowska - Curie's National Institute of Oncology - National Research Institute	Warsaw
Portugal	Champalimaud Clinical Center	Lisboa
Portugal	Centro Hospitalar do Porto-- Hospital de Santo Antonio	Porto
Portugal	Instituto Portugues De Oncologia - Instituto Portugues de Oncologia do Porto	Porto
Spain	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	Sevilla
Spain	Virgen del Rocio University Hospital	Sevilla
Spain	Fundacion Instituto Valenciano De Oncologia	Valencia
Spain	Hospital Clinico Universitario De Valencia	Valencia
United Kingdom	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

Sponsors (9)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Breast International Group, ETOP IBCSG Partners Foundation, German Adjuvant Breast Cancer Group, Gruppo Oncologico Italiano di Ricerca Clinica, Pfizer, SOLTI Breast Cancer Research Group, Swedish Association of Breast Oncologists, UNICANCER

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	distant recurrence-free interval (D-RFI) rate		5 years after first patient inclusion
Secondary	Breast cancer specific survival		5 years after first patient inclusion
Secondary	Overall survival		5 years after first patient inclusion
Secondary	Incidence of permanent treatment discontinuation		5 years after first patient inclusion