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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Surgery; Breast Cancer Stage IV; Radiotherapy
• Intervention / Treatment: Drug: Palbociclib; Other: locoregional treatment

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cécile VISSAC-SABATIER, PhD; Phone Number: 0625155960; Email: c-vissac@unicancer.fr

Study Locations

• France
  • Angers, France, 49005
    • Institut de Cancérologie de l'Ouest-Site Paul Papin
  • Avignon, France, 84818
    • Institut Sainte Catherine
  • Caen, France
    • Centre Francois Baclesse
  • Chalon-sur-Saône, France, 71100
    • Hopital Prive Sainte Marie
  • Cholet, France, 49300
    • Ch Cholet
  • Clermont-Ferrand, France, 63000
    • Centre Jean Perrin
  • Dijon, France, 21000
    • Centre George François Leclerc
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Marseille, France, 13008
    • Hôpital St Joseph
  • Montpellier, France, 34298
    • ICM Val D'Aurelle
  • Montpellier, France, 34090
    • Hôpital saint Eloi CHU Montpellier
  • Paris, France, 75020
    • Hôpital Tenon
  • Paris, France, 75014
    • Hôpital St Joseph
  • Paris, France, 75010
    • Hôpital Saint Louis APHP
  • Paris, France, 75005
    • Institut Curie Site Paris
  • Pau, France, 64000
    • Centre Hospitalier de Pau
  • Pontoise, France, 95000
    • CH René Dubos
  • Reims, France, 51726
    • Institut Jean Godinot
  • Rennes, France, 35042
    • Centre Eugene Marquis
  • Saint Cloud, France, 92210
    • Institut Curie Hopital Rene Huguenin
  • Saint Gregoire, France, 35760
    • Hôpital Privé à Saint Grégoire
  • Sarcelles, France, 95200
    • GCS RISSA - Institut de cancérologie Paris Nord
  • Toulouse, France, 31059
    • Institut Claudius Regaud
  • Vandœuvre-lès-Nancy, France, 54519
    • Institut de Cancérologie de Lorraine
  • Villejuif, France, 94800
    • Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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).
2. 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
3. Age ≥18 years
4. Eastern Cooperative Oncology Group (ECOG) ≤2
5. Indication for treatment with palbociclib and letrozole (with or without ovarian suppression)
6. Diagnostic FFPE tumour sample and/or frozen primary breast tumour sample available
7. Women of childbearing potential must have a negative serum or urine pregnancy test done within 14 days before inclusion
8. Patients must agree to use adequate contraception methods for the duration of the study and for within 21 days after completing treatment
9. 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
10. Patient affiliated to a social security system
11. Written informed consent obtained prior to performing any protocol-related procedures including screening evaluations

Exclusion Criteria:

1. 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*
2. Women with previously diagnosed and treated ipsilateral adenocarcinoma of the breast
3. Women with previously treated or concomitant contralateral breast cancer except for Ductal carcinoma in situ (DCIS) treated with curative intent
4. Patients with another concomitant cancer
5. Concurrent enrolment in another clinical trial in which investigational therapies are administered or administration of an investigational drug within 30 days before inclusion
6. Pregnant women or women who are breast-feeding
7. Inability or willingness to swallow oral medication
8. HIV, hepatitis (B and C)
9. Active infection
10. Prior therapy for metastatic breast cancer (systemic or local)

11. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Palbociclib + locoregional treatment; All 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

Drug: Palbociclib; 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.; Other: locoregional treatment; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival rate in patients receiving the letrozole plus palbociclib combination plus locoregional treatment	Overall survival	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		60 months
Clinical response rate on both primary tumour and metastasis disease	Follow-up of the disease status by imaging exams until surgery	24 months
Pathological response rate in primary tumour	Pathological response (tumour size, cellularity... ) evaluated at the surgery or at the biopsy	26 weeks
Conversion rate of breast surgery (conservative-radical)	Rate of modification of indication of mastectomy	26 weeks
Locoregional control rate	Rate of locoregional recurrence after surgery and/or radiotherapy	60 months
Progression-free survival (PFS)	Follow-up of the disease status by imaging exams	60 months
Incidence of combined therapies in terms of adverse events	Will be evaluated using the National Cancer Institute - common terminology criteria for adverse events (NCI-CTCAE) v5.0	60 months
Registration of post letrozole-CDKi therapies	Records of cancer treatments prescribed to patients after disease progression	60 months
Evolution of quality of life during treatment	self-administered questionnaire of quality of life EORTC QLQ-C30 taking into account the patient's activity and his/her physical and psychological state	60 months
Evolution of quality of life during treatment	self-administered questionnaire of quality of life EORTC QLQ-BR23, complementary module to QLQ C30 questionnaire, is more specifically interested in patients with se cancer and the impact of treatment on their lives	60 months
Evolution of quality of life during treatment	self-administered questionnaire of quality of life Euroquol EQ-5D-5L consists of a descriptive system and a visual scale	60 months

Collaborators and Investigators

• Sponsor: UNICANCER
• Collaborators: Pfizer
• Investigators: Principal Investigator: Claire Bonneau, MD, Institut Curie

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2019
• Primary Completion (Estimated): October 23, 2024
• Study Completion (Estimated): October 23, 2027

Study Registration Dates

• First Submitted: March 6, 2019
• First Submitted That Met QC Criteria: March 11, 2019
• First Posted (Actual): March 12, 2019

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: therapies combination
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: UC-0140/1814; 2019-A00570-57 (Registry Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No