Clinical trial • Phase III • Oncology

Palbociclib for Breast cancer | Hormone receptor positive breast cancer | HER2-negative breast cancer | Locoregional recurrence of breast cancer

Phase III trial of Palbociclib for Breast cancer | Hormone receptor positive breast cancer | HER2-negative breast cancer | Locoregional recurrence of brea…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Breast cancer | Hormone receptor positive breast cancer | HER2-negative breast cancer | Locoregional recurrence of breast cancer
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
19-02-2024
First CTIS Authorization Date
04-04-2024

Trial design

Randomised, open-label, arm a: palbociclib 125 mg/day orally for 21 days, followed by 7 days rest for 3 years from randomization + standard endocrine therapy for at least 3 years from randomization; arm b: standard endocrine therapy for at least 3 years from randomization-controlled Phase III trial in Hungary, Austria, Spain and others.

Randomised
Yes
Open Label
Yes
Comparator
Arm A: Palbociclib 125 mg/day orally for 21 days, followed by 7 days rest for 3 years from randomization + standard endocrine therapy for at least 3 years from randomization; Arm B: Standard endocrine therapy for at least 3 years from randomization
Target Sample Size
381
Trial Duration For Participant
1095

Eligibility

Recruits 381 Vulnerable population selected. Written Informed Consent (IC) is required from each participant prior to randomization. Country-specific subject information sheets and informed consent forms (SIS/ICF) and addenda are provided (including versions for pregnant partner and Women of Childbearing potential) for participating countries. No procedures for assent of minors are described (participants must be 18 years or older)..

Pregnancy Exclusion
Pregnant or lactating women; lactation has to stop before randomization
Vulnerable Population
Vulnerable population selected. Written Informed Consent (IC) is required from each participant prior to randomization. Country-specific subject information sheets and informed consent forms (SIS/ICF) and addenda are provided (including versions for pregnant partner and Women of Childbearing potential) for participating countries. No procedures for assent of minors are described (participants must be 18 years or older).

Inclusion criteria

  • {"criterion_text":"- Histologically confirmed invasive breast cancer, defined as first proven ipsilateral local and/or regional recurrence of a primary invasive breast cancer in at least one of the sites below: – Breast – Chest wall including mastectomy scar and/or skin – Axillary or internal mammary lymph nodes\n- Completion of locoregional therapy: – Completion of gross excision of recurrence within 6 months prior to randomization – Completion of radiotherapy (if given) more than 2 weeks prior to randomization\n- Negative or microscopically involved margins\n- Female or male aged 18 years or older\n- ECOG performance status 0 or 1\n- Recurrent tumor must be hormone receptor positive: ER+ and/or PgR+ ≥1% by IHC\n- Recurrent tumor must be HER2-negative (0, 1+, 2+ by IHC and/or ISH/FISH not amplified) Tumor with HER2 status 2+ by IHC must also be negative (not amplified) by ISH/FISH\n- Normal hematological, renal, and liver function\n- The patient agrees to make tumor (diagnostic core biopsy or surgical specimen of ILRR) available for submission for central pathology review\n- Patients must either be planned to initiate, or have already started, endocrine therapy for ipsilateral isolated locoregional recurrence\n- Written Informed Consent (IC) prior to randomization"}

Exclusion criteria

  • {"criterion_text":"- Recurrence of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules) not surgically removable\n- Evidence of distant metastasis as based on conventional staging examinations (physical, chest X-ray or CT, abdominal ultrasound or CT, bone scintigraphy or FDG-PET-CT).\n- Bilateral synchronous or metachronous invasive breast cancer (in situ carcinoma of the contralateral breast is allowed)\n- Inflammatory breast cancer\n- Patients with a history of malignancy, other than invasive breast cancer, with the following exceptions: – Patients diagnosed, treated and disease-free for at least 5 years and deemed by the investigator to be at low risk for recurrence of that malignancy are eligible – Patients with the following malignancies are eligible, even if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast; cervical cancer in situ; thyroid cancer in situ; non-metastatic, non-melanomatous skin cancers\n- Previous treatment with palbociclib or any other CDK 4/6 inhibitors\n- Previous or planned chemotherapy or planned radiotherapy for the ipsilateral isolated locoregional recurrence (radiotherapy is allowed, but must be completed more than 2 weeks prior to randomization)\n- Concurrent disease or condition that would make the patient inappropriate for study participation or any serious medical disorder that would interfere with the patient’s safety\n- Contraindications or known hypersensitivity to the palbociclib or excipients\n- History of extensive disseminated/bilateral or known presence of interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and pulmonary fibrosis. History of prior radiation pneumonitis is not an exclusion criterion.\n- Pregnant or lactating women; lactation has to stop before randomization"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary endpoint iDFS is defined as duration of time from randomization until first appearance of invasive local, regional, or distant recurrence (including invasive ipsilateral breast tumor recurrence), invasive contralateral breast cancer, a second (non-breast) invasive cancer, or death from any cause.","definition_or_measurement_approach":"iDFS is defined as duration of time from randomization until first appearance of invasive local, regional, or distant recurrence (including invasive ipsilateral breast tumor recurrence), invasive contralateral breast cancer, a second (non-breast) invasive cancer, or death from any cause."}

Secondary endpoints

  • {"endpoint_text":"- Adverse events, according to CTCAE version 5\n- Breast cancer-free interval (BCFI)\n- Distant recurrence-free interval (DRFI)\n- Overall survival (OS)","definition_or_measurement_approach":"Adverse events: graded according to CTCAE version 5. BCFI, DRFI and OS are listed as time-to-event endpoints (definitions not further specified in the available text)."}

Recruitment

Planned Sample Size
381
Recruitment Window Months
90
Consent Approach
Written Informed Consent (IC) required prior to randomization. Country-specific subject information sheets and ICFs are provided in multiple language versions and with addenda (including pregnant partner and Women of Childbearing potential versions). Consent is obtained from the participant; no assent for minors is described as minimum age is 18 years.

Geography

Total Number Of Sites
38
Total Number Of Participants
381

Hungary

Earliest CTIS Part Ii Submission Date
29-02-2024
Latest Decision Or Authorization Date
05-05-2025
Processing Time Days
431
Number Of Sites
1
Number Of Participants
30

Sites

Site Name
National Institute of Oncology
Department Name
Medical oncology
Principal Investigator Name
Gabor Rubovszky
Principal Investigator Email
garub@oncol.hu
Contact Person Name
Gabor Rubovszky
Contact Person Email
garub@oncol.hu
Number Of Participants
30

Austria

Earliest CTIS Part Ii Submission Date
29-02-2024
Latest Decision Or Authorization Date
31-03-2025
Processing Time Days
396
Number Of Sites
3
Number Of Participants
20

Sites

Site Name
Medical University Of Graz
Department Name
Medical Oncology
Principal Investigator Name
Christoph Suppan
Principal Investigator Email
christoph.suppan@medunigraz.at
Contact Person Name
Christoph Suppan
Contact Person Email
christoph.suppan@medunigraz.at
Site Name
Medizinische Universitaet Innsbruck
Department Name
Medical oncology
Principal Investigator Name
Daniel Egle
Principal Investigator Email
daniel.egle@tirol-kliniken.at
Contact Person Name
Daniel Egle
Contact Person Email
daniel.egle@tirol-kliniken.at
Site Name
SCRI CCCIT Ges.m.b.H.
Department Name
Medical Oncology
Principal Investigator Name
Simon Peter Gampenrieder
Principal Investigator Email
s.gampenrieder@salk.at
Contact Person Name
Simon Peter Gampenrieder
Contact Person Email
s.gampenrieder@salk.at

Spain

Earliest CTIS Part Ii Submission Date
29-02-2024
Latest Decision Or Authorization Date
07-05-2025
Processing Time Days
433
Number Of Sites
13
Number Of Participants
141

Sites

Site Name
Hospital General Universitario Dr. Balmis
Department Name
Medical Oncology
Principal Investigator Name
Jose Ponce Lorenzo
Principal Investigator Email
JOSEPONCE.ONCOALICANTE@GMAIL.COM
Contact Person Name
Jose Ponce Lorenzo
Site Name
Hospital Universitario Virgen De La Macarena
Department Name
Medical Oncology
Principal Investigator Name
Esteban Nogales Fernández
Principal Investigator Email
esteban.nogales@gmail.com
Contact Person Name
Esteban Nogales Fernández
Contact Person Email
esteban.nogales@gmail.com
Site Name
Institut Catala D'oncologia (L'Hospitalet De Llobregat)
Department Name
Medical Oncology
Principal Investigator Name
Rafael Villanueva Vazquez
Principal Investigator Email
ravillanueva@iconcologia.net
Contact Person Name
Rafael Villanueva Vazquez
Contact Person Email
ravillanueva@iconcologia.net
Site Name
Hospital Universitario Basurto
Department Name
Medical Oncology
Principal Investigator Name
Elena Gleve Calvo
Principal Investigator Email
ELENA.GALVECALVO@OSAKIDETZA.EUS
Contact Person Name
Elena Gleve Calvo
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Medical Oncology
Principal Investigator Name
Noelia Martinez
Principal Investigator Email
mjnoelia@hotmail.com
Contact Person Name
Noelia Martinez
Contact Person Email
mjnoelia@hotmail.com
Site Name
Hospital Universitario 12 De Octubre
Department Name
Medical Oncology
Principal Investigator Name
Eva Ciruelos
Principal Investigator Email
eva.ciruelos@gmail.com
Contact Person Name
Eva Ciruelos
Contact Person Email
eva.ciruelos@gmail.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Medical Oncology
Principal Investigator Name
Meritxell Bellet
Principal Investigator Email
mbellet@vhio.net
Contact Person Name
Meritxell Bellet
Contact Person Email
mbellet@vhio.net
Site Name
Hospital Universitario De Canarias
Department Name
Medical Oncology
Principal Investigator Name
Josefina Cruz Jurado
Principal Investigator Email
jcruzjurado@gmail.com
Contact Person Name
Josefina Cruz Jurado
Contact Person Email
jcruzjurado@gmail.com
Site Name
Fundacion Instituto Valenciano De Oncologia
Department Name
Medical Oncology
Principal Investigator Name
Joaquin Gauila
Principal Investigator Email
jogagre@hotmail.com
Contact Person Name
Joaquin Gauila
Contact Person Email
jogagre@hotmail.com
Site Name
Institut Catala D'oncologia (Girona)
Department Name
Medical Oncology
Principal Investigator Name
Sonia del Barco Berrón
Principal Investigator Email
sdelbarco@iconcologia.net
Contact Person Name
Sonia del Barco Berrón
Contact Person Email
sdelbarco@iconcologia.net
Site Name
Hospital Unviersitario Miguel Servet
Department Name
Medical Oncology
Principal Investigator Name
Antonino Anton
Principal Investigator Email
aantont@gmail.com
Contact Person Name
Antonino Anton
Contact Person Email
aantont@gmail.com
Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Medical Oncology
Principal Investigator Name
María Eva Pérez López
Principal Investigator Email
MARIA.EVA.PEREZ.LOPEZ@sergas.es
Contact Person Name
María Eva Pérez López
Site Name
Hospital Universitario Virgen De La Victoria
Department Name
Medical Oncology
Principal Investigator Name
Nuria Ribelles
Principal Investigator Email
nuriaribelles@gmail.com
Contact Person Name
Nuria Ribelles
Contact Person Email
nuriaribelles@gmail.com

Italy

Earliest CTIS Part Ii Submission Date
29-02-2024
Latest Decision Or Authorization Date
24-06-2025
Processing Time Days
481
Number Of Sites
10
Number Of Participants
160

Sites

Site Name
Istituti Clinici Scientifici Maugeri (Pavia)
Department Name
Medical Oncology
Principal Investigator Name
Laura Deborah Locati
Principal Investigator Email
lauradeborah.locati@icsmaugeri.it
Contact Person Name
Laura Deborah Locati
Site Name
European Institute Of Oncology S.r.l. (Milan)
Department Name
Medical Oncology
Principal Investigator Name
Elisabetta Munzone
Principal Investigator Email
elisabetta.munzone@ieo.it
Contact Person Name
Elisabetta Munzone
Contact Person Email
elisabetta.munzone@ieo.it
Site Name
Azienda USL Toscana Centro (Prato)
Department Name
Medical Oncology
Principal Investigator Name
Laura Biganzoli
Principal Investigator Email
laura.biganzoli@uslcentro.toscana.it
Contact Person Name
Laura Biganzoli
Site Name
UOC ONCOLOGIA MEDICA - P.O. "A. PERRINO" (Brindisi)
Department Name
Medical oncology
Principal Investigator Name
Sverio Cinieri
Principal Investigator Email
saverio.cinieri@ieo.it
Contact Person Name
Sverio Cinieri
Contact Person Email
saverio.cinieri@ieo.it
Site Name
Centro Di Riferimento Oncologico Di Aviano
Department Name
Medical Oncology
Principal Investigator Name
Simon Spazzapan
Principal Investigator Email
spazzapan@cro.it
Contact Person Name
Simon Spazzapan
Contact Person Email
spazzapan@cro.it
Site Name
Azienda Unita Sanitaria Locale Della Romagna (Rimini)
Department Name
Medical Oncology
Principal Investigator Name
Lorenzo Gianni
Principal Investigator Email
lorenzo.gianni@auslromagna.it
Contact Person Name
Lorenzo Gianni
Contact Person Email
lorenzo.gianni@auslromagna.it
Site Name
Osppedali Riuniti di Bergamo
Department Name
Medical Oncology
Principal Investigator Name
Alberto Zambelli
Principal Investigator Email
azambelli@asst-pg23.it
Contact Person Name
Alberto Zambelli
Contact Person Email
azambelli@asst-pg23.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l. (Meldola)
Department Name
Medical Oncology
Principal Investigator Name
Samanta Sarti
Principal Investigator Email
samanta.sarti@irst.emr.it
Contact Person Name
Samanta Sarti
Contact Person Email
samanta.sarti@irst.emr.it
Site Name
Azienda Ospedaliero-Universitaria Maggiore Della Carita (Novara)
Department Name
Medical Oncology
Principal Investigator Name
Alessandra Gennari
Principal Investigator Email
alessandra.gennari@maggioreosp.novara.it
Contact Person Name
Alessandra Gennari
Site Name
Azienda Ospedaliero Universitaria Parma
Department Name
Medical Oncology
Principal Investigator Name
Daniela Boggiani
Principal Investigator Email
Boggiani@ao.pr.it
Contact Person Name
Daniela Boggiani
Contact Person Email
Boggiani@ao.pr.it

France

Earliest CTIS Part Ii Submission Date
29-02-2024
Latest Decision Or Authorization Date
18-08-2025
Processing Time Days
536
Number Of Sites
11
Number Of Participants
30

Sites

Site Name
Institut Gustave Roussy
Department Name
Medical Oncology
Principal Investigator Name
Barbara Pistilli
Principal Investigator Email
BARBARA.PISTILLI@gustaveroussy.fr
Contact Person Name
Barbara Pistilli
Site Name
Groupe Hospitalier Bretagne Sud (Lorient)
Department Name
Medical Oncology
Principal Investigator Name
Edwina Girard
Principal Investigator Email
e.girard@ghbs.bzh
Contact Person Name
Edwina Girard
Contact Person Email
e.girard@ghbs.bzh
Site Name
Polyclinique Bordeaux Nord Aquitaine
Department Name
Medical Oncology
Principal Investigator Name
Nadine Dohollou
Principal Investigator Email
n.dohollou@bordeauxnord.com
Contact Person Name
Nadine Dohollou
Contact Person Email
n.dohollou@bordeauxnord.com
Site Name
Centre Hospitalier Et Universitaire De Limoges
Department Name
Medical Oncology
Principal Investigator Name
Laurene Venat-Bouvet
Principal Investigator Email
laurence.venat-bouvet@chu-limoges.fr
Contact Person Name
Laurene Venat-Bouvet
Site Name
Institut Sainte Catherine (Avignon)
Department Name
Medical Oncology
Principal Investigator Name
Julien Grenier
Principal Investigator Email
j.grenier@isc84.org
Contact Person Name
Julien Grenier
Contact Person Email
j.grenier@isc84.org
Site Name
Centre Leon Berard (Lyon)
Department Name
Medical Oncology
Principal Investigator Name
Thomas Bachelot
Principal Investigator Email
thomas.bachelot@lyon.unicancer.fr
Contact Person Name
Thomas Bachelot
Site Name
Institut Bergonie (Bordeaux)
Department Name
Medical Oncology
Principal Investigator Name
Camille Chakiba-Brugere
Principal Investigator Email
c.chakiba@bordeaux.unicancer.fr
Contact Person Name
Camille Chakiba-Brugere
Site Name
Centre Francois Baclesse (Caen)
Department Name
Medical Oncology
Principal Investigator Name
Christelle Levy
Principal Investigator Email
c.levy@baclesse.unicancer.fr
Contact Person Name
Christelle Levy
Contact Person Email
c.levy@baclesse.unicancer.fr
Site Name
Centre Antoine Lacassagne (Nice)
Department Name
Medical Oncology
Principal Investigator Name
Jean-Marc Ferrero
Principal Investigator Email
jean-marc.ferrero@nice.unicancer.fr
Contact Person Name
Jean-Marc Ferrero
Site Name
Centre Hospitalier De Cholet
Department Name
Medical Oncology
Principal Investigator Name
Victor Simmet
Principal Investigator Email
victor.simmet@gmail.com
Contact Person Name
Victor Simmet
Contact Person Email
victor.simmet@gmail.com
Site Name
Institut De Cancerologie Strasbourg Europe
Department Name
Medical Oncology
Principal Investigator Name
Thierry Petit
Principal Investigator Email
t.petit@icans.eu
Contact Person Name
Thierry Petit
Contact Person Email
t.petit@icans.eu

Sponsor

Primary sponsor

Full Name
ETOP IBCSG Partners Foundation
Organisation Type
Laboratory/Research/Testing facility
Country Of Registered Address
Switzerland

Third parties

  • {"country":"United States","full_name":"Frontier Science & Technology Research Foundation Inc.","duties_or_roles":"sponsorDuties code 6","organisation_type":"Pharmaceutical company"}
  • {"country":"Italy","full_name":"IBCSG Central Pathology Office and Laboratory at European Institute of Oncology","duties_or_roles":"sponsorDuties code 4","organisation_type":"Health care"}
  • {"country":"United States","full_name":"Dana-Farber Cancer Institute Inc.","duties_or_roles":"sponsorDuties code 10","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties code 15; Palbociclib: drug labeling distribution to site","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
IBRANCE 125 mg film-coated tablets
Active Substance
Palbociclib
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (marketing authorisation present)
Starting Dose
125 mg/day orally for 21 days, followed by 7 days rest (per 28-day cycle)
Dose Levels
75 mg; 100 mg; 125 mg
Frequency
21 days on, 7 days off (per 28-day cycle)
Maximum Dose
125 mg/day
Investigational Product Name
IBRANCE 100 mg film-coated tablets
Active Substance
Palbociclib
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (marketing authorisation present)
Starting Dose
125 mg/day orally for 21 days, followed by 7 days rest (dose reductions available as per protocol)
Dose Levels
75 mg; 100 mg; 125 mg
Frequency
21 days on, 7 days off (per 28-day cycle)
Maximum Dose
125 mg/day
Investigational Product Name
IBRANCE 75 mg film-coated tablets
Active Substance
Palbociclib
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (marketing authorisation present)
Starting Dose
125 mg/day orally for 21 days, followed by 7 days rest (dose reductions available as per protocol)
Dose Levels
75 mg; 100 mg; 125 mg
Frequency
21 days on, 7 days off (per 28-day cycle)
Maximum Dose
125 mg/day
Investigational Product Name
IBRANCE 75 mg hard capsules
Active Substance
Palbociclib
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (marketing authorisation present)
Starting Dose
125 mg/day orally for 21 days, followed by 7 days rest (dose reductions available as per protocol)
Dose Levels
75 mg; 100 mg; 125 mg
Frequency
21 days on, 7 days off (per 28-day cycle)
Maximum Dose
125 mg/day
Investigational Product Name
IBRANCE 125 mg hard capsules
Active Substance
Palbociclib
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (marketing authorisation present)
Starting Dose
125 mg/day orally for 21 days, followed by 7 days rest (per 28-day cycle)
Dose Levels
75 mg; 100 mg; 125 mg
Frequency
21 days on, 7 days off (per 28-day cycle)
Maximum Dose
125 mg/day
Investigational Product Name
IBRANCE 100 mg hard capsules
Active Substance
Palbociclib
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (marketing authorisation present)
Starting Dose
125 mg/day orally for 21 days, followed by 7 days rest (dose reductions available as per protocol)
Dose Levels
75 mg; 100 mg; 125 mg
Frequency
21 days on, 7 days off (per 28-day cycle)
Maximum Dose
125 mg/day
Combination Treatment
Yes

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