Locoregional Treatment and Palbociclib in de Novo, Treatment Naive, Stage IV ER+, HER2- Breast Cancer Patients
PALATINE
PALbociclib in Advanced Breast Cancer: Therapy INtegrating locorEgional Treatment and Palbociclib in de Novo, Treatment Naive, Stage IV ER+, HER2- Breast Cancer Patients
2 other identifiers
interventional
200
1 country
26
Brief Summary
Approximately 3.5% to 6% of newly diagnosed breast cancer patients are stage IV metastatic. De novo metastatic breast cancer accounts for 20% to 25% of these cases. Despite a decrease in mortality in Europe and North America due to early detection and access to treatment, breast cancer remains the 2ⁿᵈ leading cause of cancer deaths in developed countries after lung cancer and the world's leading cause. In the ESME French national retrospective cohort (NCT03275311), the newly diagnosed estrogen receptor (ER)-positive and HER2-negative (luminal) metastatic patients had a 59.1 months overall survival (OS) for pre-menopausal women and 44.7 months for postmenopausal women. In the same cohort, the median OS was 47.4 months for de novo metastatic patients with hormone receptor (HR)-positive / HER2-negative breast cancer. The most important current treatment for metastatic breast cancer remains systemic therapy. Surgery and radiation are mainly used to treat symptoms. However, more than 15 retrospective studies have assessed the impact of locoregional treatment on relapse and OS. These studies suggested an improvement of the OS in patients with de novo metastatic breast cancer thanks to the addition of locoregional treatment to systemic therapy. Recent data from the ESME cohort suggest that patients with de novo luminal or HER2-positive metastatic breast cancer may benefit from local treatment of the primary tumor. Several prospective trials have attempted to demonstrate the benefit of locoregional treatment with mixed results. This can be explained by a limited power of statistical analysis, on the recruitment of patients with breast cancer of all types, and on a limited access to effective systemic therapies in some cases and all before the area of anti CD4/6 which is the current standard treatment in patients with HR-positive / HER2-negative luminal metastatic disease. However, guidelines indicate that a "multimodal approach, including curative locoregional treatments, should be considered". As a result, many clinicians offer locoregional treatment of the primary tumor, especially if there is a good response to the first line of systematic treatment. Taken together, these data underscore the need for an evaluation of the value of combined therapy - endocrine therapy - CDK4/6 inhibitor and locoregional treatment - in this population of patients with newly diagnosed HR-positive / HER2-negative breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Oct 2019
Longer than P75 for not_applicable
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 6, 2019
CompletedFirst Posted
Study publicly available on registry
March 12, 2019
CompletedStudy Start
First participant enrolled
October 23, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 18, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 23, 2027
ExpectedMay 20, 2026
April 1, 2026
4.8 years
March 6, 2019
May 18, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall survival rate in patients receiving the letrozole plus palbociclib combination plus locoregional treatment
Overall survival
24 months
Secondary Outcomes (11)
Clinical response rate on both primary tumour and metastasis disease
24 months
Pathological response rate in primary tumour
26 weeks
Conversion rate of breast surgery (conservative-radical)
26 weeks
Locoregional control rate
60 months
Progression-free survival (PFS)
60 months
- +6 more secondary outcomes
Study Arms (1)
Palbociclib + locoregional treatment
OTHERAll patients will receive the standard of care treatment ie Palbociclib + letrozole for 24-26 weeks (a delay of +/- 2 weeks to initiate the locoregional treatment is authorized after the day 1 of cycle 1 of palbociclib plus letrozole). After this period, patient will have the most adapted locoregional treatment ie surgery (conservative or mastectomy) with or without radiotherapy, or radiotherapy. The palbociclib will be continued until progression
Interventions
The included patients will first receive the following systemic treatment according standard of care: * Non-steroidal aromatase inhibitor (letrozole) * Palbociclib * Monthly Luteinizing hormone-releasing hormone (LHRH) analogue for non-menopausal patients only. Surgical bilateral oophorectomy is an acceptable option.
After normally 6 courses of systemic treatment initiation, the loco-regional treatment of the primary tumour will be performed: surgery (conservative or mastectomy) with or without radiotherapy, or radiotherapy
Eligibility Criteria
You may qualify if:
- Women with newly diagnosed and histologically proven de novo adenocarcinoma of the breast, Any T, any N, with at least one metastatic site measurable and/or non-measurable according to Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 and/or PET Response Criteria in Solid Tumours (PERCIST) v1.0 and/or MD Anderson bone response criteria (MDA criteria). For patients with only bone metastases, at least one lytic and non-irradiated lesion must be present NB: Bilateral breast cancer is allowed only if tumours present similar histological criteria (morphological subtype, ER and HER2 status).
- Estrogen Receptor (ER)-positive and HER2-negative breast cancer. To be considered as ER-positive, the biopsy of the primary tumour must display at least 10% of cancer cells with positive ER staining. HER2-positive is defined as IHC3+ or FISH/CISH amplified according to 2018 criteria
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) ≤2
- Indication for treatment with palbociclib and letrozole (with or without ovarian suppression)
- Diagnostic FFPE tumour sample and/or frozen primary breast tumour sample available
- Patients must agree to use adequate contraception methods for the duration of the study and for within 21 days after completing treatment
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and any protocol-related procedures including absence of co-morbidities preventing surgery and or radiotherapy and 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
- Patient affiliated to a social security system
- Written informed consent obtained prior to performing any protocol-related procedures including screening evaluations
You may not qualify if:
- Patients with advanced, symptomatic, visceral spread at a risk for short-term, life-threatening complications according to investigator judgement and at risk for visceral crisis as defined by ABC4\*
- Women with previously diagnosed and treated ipsilateral adenocarcinoma of the breast
- Women with previously treated or concomitant contralateral breast cancer except for Ductal carcinoma in situ (DCIS) treated with curative intent
- Patients with another concomitant cancer
- Pregnant women or women who are breast-feeding
- Inability or willingness to swallow oral medication
- HIV, hepatitis (B and C)
- Active infection
- Prior therapy for metastatic breast cancer (systemic or local)
- Persons deprived of their freedom or under guardianship or incapable of giving consent
- Visceral crisis is defined as severe organ dysfunction as assessed by signs and symptoms, laboratory studies and rapid progression of disease. Visceral crisis is not the mere presence of visceral metastases but implies important visceral compromise leading to a clinical indication for a more rapidly efficacious therapy, particularly since another treatment option at progression will probably not be possible.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (26)
Institut de Cancérologie de l'Ouest-Site Paul Papin
Angers, 49005, France
Institut Sainte Catherine
Avignon, 84818, France
Centre François Baclesse
Caen, France
Hôpital privé sainte Marie
Chalon-sur-Saône, 71100, France
CH Cholet
Cholet, 49300, France
Centre Jean Perrin
Clermont-Ferrand, 63000, France
Centre George François Leclerc
Dijon, 21000, France
Centre Léon Bérard
Lyon, 69008, France
Hôpital St Joseph
Marseille, 13008, France
Institut Paoli Calmettes
Marseille, 13009, France
Hôpital saint Eloi CHU Montpellier
Montpellier, 34090, France
ICM Val d'Aurelle
Montpellier, 34298, France
Institut Curie Site Paris
Paris, 75005, France
Hôpital Saint Louis APHP
Paris, 75010, France
Hôpital St Joseph
Paris, 75014, France
Hôpital Tenon
Paris, 75020, France
Centre Hospitalier de Pau
Pau, 64000, France
CH René Dubos
Pontoise, 95000, France
Institut Jean Godinot
Reims, 51726, France
Centre Eugène Marquis
Rennes, 35042, France
Institut Curie Hôpital René Huguenin
Saint-Cloud, 92210, France
Hôpital Privé à Saint Grégoire
Saint-Grégoire, 35760, France
GCS RISSA - Institut de cancérologie Paris Nord
Sarcelles, 95200, France
Institut Claudius Regaud
Toulouse, 31059, France
Institut de Cancérologie de Lorraine
Vandœuvre-lès-Nancy, 54519, France
Gustave Roussy
Villejuif, 94800, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Claire Bonneau, MD
Institut Curie
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 6, 2019
First Posted
March 12, 2019
Study Start
October 23, 2019
Primary Completion
August 18, 2024
Study Completion (Estimated)
October 23, 2027
Last Updated
May 20, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
- Access Criteria
- Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.
Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.