Clinical trial NCT06805812: Predicting clinicAL outcoMes During First-line CDK4/6 Inhibitors Plus Endocrine Therapy in Patients With Advanced Hormone REceptor-poSitive HER2-negative Breast Cancer: the Retrospective-prospective Multicenter Italian PALMARES-2 Study
Official title: Predictive Impact of Peripheral Blood Lymphocytes on clinicAL outcoMes During First-line CDK4/6 Inhibitors Plus Endocrine Therapy in Patients With Advanced Hormone REceptor-poSitive HER2-negative Breast Cancer: the Retrospective-prospective Multicenter Italian PALMARES-2 Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Adenocarcinoma
Breast Cancer Stage IV
Breast Cancer, Metastatic
Breast Carcinoma
Breast Diseases
Breast Neoplasms
Breast Neoplasms, Male
Breast Cancer
Breast Cancer With Metastatic Bone Disease
Breast Cancers
Breast Neoplasm
Breast Tumors
HR+ HER2- Men, Pre/Postmenopausal Advanced Breast Cancer
HR+ Advanced or Metastatic Breast Cancer
HR+/HER2- Breast Cancer
HRpos Breast Neoplasms
HR-positive, HER2-negative Advanced Breast Cancer
HR-positive, HER2-negative and PIK3CA Mutation Advanced Breast Cancer
HR-positive Breast Cancer
Hormone Receptor-Positive Breast Cancer
Hormone Receptor Positive Breast Adenocarcinoma
Hormone Receptor Positive Breast Carcinoma
Hormone Receptor Positive Breast Neoplasms
Hormone Receptor Positive HER-2 Negative Breast Cancer
Hormone Receptor Positive Malignant Neoplasm of Breast
Hormone Receptor Positive Metastatic Breast Cancer
Hormone Receptor Positive, HER2 Negative Breast Cancer
Hormone Receptor Negative Breast Cancer
Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer
Hormone Receptor Positive Breast Cancer
Hormone Receptor Positive (ER+/PR+, and Her2-) Metastatic Breast Cancer
Hormone Receptor Positive, HER2-negative Neoplasms
Hormone Receptor Positive, HER2-low Neoplasms
Hormone Receptor Positive (HR+), HER2-negative Breast Cancer
Hormone Receptor (HR)-Positive Breast Cancer
Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer
Palbociclib
Ribociclib
Abemaciclib
CDK4/6 Inhibitor
CDK4/6 Inhibitors
Keywords: HR+/HER2- Advanced Breast Cancer
HR+/HER2- Metastatic Breast Cancer
Palbociclib
Ribociclib
Abemaciclib
CDK4/6i
Cyclin-Dependent Kinase 4/6 inhibitors
Metastatic Breast Cancer
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Sponsor class: OTHER
Collaborators: name: European Institute of Oncology, Italy
name: Humanitas Research Hospital IRCCS, Rozzano-Milan
name: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
name: OSPEDALE ASST CREMONA
name: IOV Oncologico Veneto Padova
name: ASST Fatebenefratelli Sacco
name: IRCCS Fondazione Salvatore Maugeri, Pavia, Italy
name: IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori Meldola
name: Azienda Ospedaliero-Universitaria di Modena
name: Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara
name: A.O.U. Federico II, Napoli
name: San Raffaele University Hospital, Italy
name: Centro di Riferimento Oncologico - Aviano
name: Azienda Socio-Sanitaria Territoriale Lariana
name: Azienda ULSS 3 Serenissima, Ospedale di Mirano
name: Azienda Ospedaliero Universitaria Policlinico Umberto I, Roma
name: Fondazione IRCCS Policlinico San Matteo di Pavia
name: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
name: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
name: Azienda Ospedaliero-Universitaria Careggi
name: Humanitas, Istituto Clinico Catanese
name: Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale
name: Fondazione Policlinico Universitario Campus Bio-Medico
name: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
First posted: 2025-02-03
Enrollment: 3500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: The study involves the retrospective and prospective collection of consecutive HR+/HER2- advanced Breast Cancer patients (defined as metastatic or locally advanced not candidate for definitive curative intervention) treated with CDK4/6i in combination with endocrine therapy as first-line treatment for advanced disease in different Italian cancer centers.

Brief summary: PALMARES-2 is a retrospective/prospective, observational, multicenter, population-based study, aiming at providing real-world evidences on HR+/HER2- aBC patients treated with first-line CDK4/6i plus ET. The present study has the objective to collect data coming from different sources, i.e. RWD, medical images and biological samples, from patients treated with CDK4/6i as first-line of therapy for HR+/HER2- aBC. In consideration of the complexity of data collected and different objectives of the study, this master protocol foresees different sub-studies, which encompasses different methodologies for data collection, data extraction and analyses.

Detailed description: The PALMARES-2 study aims to collect data from different sources, i.e. real-world clinical data, medical images and biological data and samples, from patients treated with CDK4/6i as first-line therapy for patients with HR+/HER2- advanced breast cancer. Due to the complexity of the data collected and the different objectives of the study, this protocol includes several sub-studies, which include different methodologies for data collection, extraction and analysis:

* The first sub-study (RWD sub-study) will aim to collect real-world clinical data of patients who received ET+CDK4/6i in the first-line setting; the primary objective of this sub-study is to assess whether there is a difference in OS between the three CDK4/6i in the real-world population, while secondary objectives include comparisons in specific sub-groups;
* The second sub-study (Safety sub-study) includes the collection of comorbidities, concomitant medications and toxicities of patients enrolled in the study; the primary objective of this sub-study is to evaluate the difference in severe toxicity between the three CDK4/6i in the real-world population
* The third sub-study (medical imaging sub-study) consists of the collection of computed tomography (CT) and fluorodeoxyglucose positron emission tomography (FdG-PET) images at baseline and digitised haematoxylin-eosin (HE) slides to build a multi-omics predictive model;
* The fourth sub-study (translational sub-study) aims to collect tumour samples from a proportion of patients enrolled in the study to perform genomics and transcriptomics analyses; information from this data source will be integrated into the model built with the previous data to further improve the performance of the previous model
* The fifth sub-study (subsequent lines sub-study) focuses on the lines of treatment administered to patients enrolled in the study at the time of progression after first-line treatment with ET+CDK4/6i, with the aim of building predictive models of response to subsequent lines of treatment, capable of supporting oncologists' and patients' decisions in this context.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of HR+/HER2- advanced Breast Cancer (aBC), as defined as at least 1% estrogen receptor (ER) and/or progesterone receptor (PgR) positivity at IHC. HER2 negativity is defined on the basis of an IHC score of 0, 1+, or 2+ with absence of gene amplification at in situ hybridization (ISH) analyses.
* Have received or are candidate to receive treatment with palbociclib, ribociclib or abemaciclib in combination with endocrine therapy as first-line treatment for HR+/HER2- aBC.

Exclusion Criteria:

* Less than 3 months of follow up from the CDK4/6i start to the date of data cut-off;
* Have received CDK4/6i as monotherapy;
* Have received CDK4/6i as adjuvant treatment for localized disease.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From the first-line treatment start to date of any-cause death or last follow up, up to 120 months
Secondary outcomes:
measure: Real-world Progression-Free Survival (rwPFS)
timeFrame: From the start of first-line treatment to date of disease progression documented in patient medical charts or death or last follow up, whichever occurs first, up to 120 months
measure: Time To Next Treatment or Death (TTNT-D)
timeFrame: From the start of first-line treatment to date of subsequent therapy start or death or last follow up, whichever occurs first, up to 120 months
measure: Time To Chemotherapy or Death (TTC-D)
timeFrame: From the start of first-line treatment to date of first chemotherapy for advanced disease start or death or last follow up, whichever occurs first, up to 120 months
Other outcomes:
Locations:
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico IRCCS
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili
city: Catania
country: Italy
facility: Humanitas Istituto Clinico Catanese
city: Como
country: Italy
facility: ASST Lariana - Ospedale Sant'Anna
city: Cremona
country: Italy
facility: ASST Ospedale Maggiore
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Genova
country: Italy
facility: Ospedale San Martino
city: Meldola
country: Italy
facility: Istituto Tumori della Romagna IRST IRCCS
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Milano
country: Italy
facility: Ospedale ASST Fatebenefratelli Sacco
city: Mirano
country: Italy
facility: ULSS 3 Veneto
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria
city: Napoli
country: Italy
facility: Azienda Ospedaliero-Universitaria Federico II
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
city: Novara
country: Italy
facility: Ospedale Maggiore della Carità
city: Padova
country: Italy
facility: IOV Istituto Oncologico Veneto IRCCS
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Pavia
country: Italy
facility: IRCCS - ICS Maugeri
city: Roma
country: Italy
facility: Clinica Ospedaliero - Universitaria Policlinico Umberto I
city: Roma
country: Italy
facility: Policlinico Universitario Campus Bio-Medico
city: Roma
country: Italy
facility: Policlinico Universitario Fondazione Agostino Gemelli
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
Study officials:
References: