Detail Article

Informations générales (source: ClinicalTrials.gov)

Numéro NCT

NCT03820830 Active, sans recrutement

Titre

A Phase III Open-label, Multicenter, Randomized Trial of Adjuvant Palbociclib in Combination With Endocrine Therapy Versus Endocrine Therapy Alone for Patients With Hormone Receptor Positive / HER2-negative Resected Isolated Locoregional Recurrence of Breast Cancer

Type

Interventional

Pathologie

Tumeurs du sein
Récidive

Phase

Phase 3

Promoteur

ETOP IBCSG Partners Foundation (Voir sur ClinicalTrials)

Date de début

août 2019

Date de fin

janvier 2029

Dernière mise à jour

13 septembre 2025

Résumé

POLAR is a phase III clinical trial, which will test the safety and efficacy of an investigational combination of drugs to learn whether the combination of drugs works for a specific cancer. Palbociclib (Ibrance®) is the name of the investigational agent, which is assessed together with standard anti-hormone therapy in this study. Palbociclib is used to treat patients with hormone receptor-positive / HER2-negative breast cancer which has spread beyond the original tumor and/or to other organs. During this study, anti-hormone therapy will consist of either a selective estrogen receptor modulator (such as tamoxifen) or an aromatase inhibitor (anastrozole, letrozole, exemestane) or fulvestrant (Faslodex®). Premenopausal women and men may also receive a drug called an LHRH (luteinizing hormone-releasing hormone) agonist by injection. It is standard of care for people with hormone receptor positive breast cancer to take anti-hormone therapy. The study doctor will determine the type of standard anti-hormone therapy that will be given during this trial. The purpose of the POLAR study is to compare the effect of using 3 years of palbociclib in combination with standard anti-hormone therapy with standard anti-hormone therapy alone and to evaluate the time until the breast cancer returns, if it does return.

Détail

Voir le détail Local or regional recurrence of breast cancer after mastectomy or lumpectomy indicates a poor prognosis, and accompanies or precedes distant metastasis in a high proportion of patients. Patients with isolated locoregional recurrences (ILRR), without evidence of distant metastasis hold a substantial risk of developing subsequent distant metastasis, with 5-year survival probabilities ranging between 45% and 80% after locoregional recurrence. These outcomes show the powerful negative prognostic importance of ILRR events and the need for treatments beyond surgical removal of the ILRR. Adjuvant chemotherapy and endocrine therapies reduce the risk of relapse and death in patients with primary breast cancer. However, few data are available to inform the recommendation of systemic treatment for locoregional recurrence. The International Breast Cancer Studies Group carried out the CALOR trial, Chemotherapy as Adjuvant for Locally Recurrent breast cancer (IBCSG 27-02 / BIG 1-02 / NSABP B-37), in collaboration with the Breast International Group (BIG) and the National Surgical Adjuvant Breast and Bowel Project (NSABP), to establish whether chemotherapy improves the outcome of patients with ILRR. An updated, final analysis of CALOR after median follow-up of about 9 years was published in the Journal of Clinical Oncology in April 2018, which confirmed chemotherapy benefitted patients with resected ER-negative ILRR and did not support the use of chemotherapy for ER-positive ILRR. CALOR results strongly suggest that tailoring treatment according to the disease characteristics of the recurrent lesion, in this case ILRR, provides a better indication of the possible responsiveness to treatment than relying on the characteristics of the primary tumor. Palbociclib has been granted FDA approval in the U.S. for the treatment of HR-positive/HER2-negative advanced breast cancer in combination with the hormonal treatments letrozole and fulvestrant given the unprecedented results in terms of efficacy of two pivotal clinical trials (PALOMA-2 and PALOMA-3). Palbociclib and other CDK4/6 inhibitors have also shown a good toxicity profile and therefore are ideal candidates for combination with hormonal therapy. CDK4/6 pathway activation is a well-known mechanism of resistance to endocrine therapy, indeed CDK4/6 inhibitors have shown activity in cellular models of acquired resistance to endocrine therapies. The reason for prolonged duration of palbociclib in the adjuvant setting (2 years) comes from the evidence of preclinical studies where cell senescence was investigated as an appealing mechanism of cell death and was indeed observed in vitro after exposure of breast cancer cells and tumors to a combination of endocrine therapy and palbociclib. It is therefore hypothesized that the longer patients receive combined treatment with palbociclib and an antiestrogen, the more likely they may derive prolonged clinical benefit. Based on the results of the CALOR trial and on strong evidence of activity of the combination of CDK4/6 inhibitors and endocrine therapy, the hypothesis of the POLAR trial is that the CDK4/6 inhibitor palbociclib in combination with endocrine therapy may be active as adjuvant therapy in patients with HR-positive/HER2-negative resected isolated locoregional recurrence of breast cancer. Fermer le détail

Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
CLCC INSTITUT GUSTAVE ROUSSY	Barbara PISTILLI	En recrutement IDF	05/06/2024 17:53:40	Contacter
Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
Centre Antoine Lacassagne - 06189 - Nice - France				Contact (sur clinicalTrials)
Centre Francois Baclesse - 14000 - Caen - France				Contact (sur clinicalTrials)
Centre Georges François Leclerc - 21079 - Dijon - France				Contact (sur clinicalTrials)
Cêntre Hospitaler de Cholet - 49300 - Cholet - France				Contact (sur clinicalTrials)
Centre Hospitalier Universitaire de Limoges - 87000 - Limoges - France				Contact (sur clinicalTrials)
Centre Leon Berard - 69008 - Lyon - France				Contact (sur clinicalTrials)
Centre Paul Strauss - Strasbourg - France				Contact (sur clinicalTrials)
Groupe hospitalier de Bretagne Sud, Hôpital du Scorff - Lorient - France				Contact (sur clinicalTrials)
ICM Val d'Aurelle - 34298 - Montpellier - France				Contact (sur clinicalTrials)
Institut Bergonie - 33076 - Bordeaux - France				Contact (sur clinicalTrials)
Institut Claudius Regaud - 31100 - Toulouse - France				Contact (sur clinicalTrials)
Institut Sainte Catherine - 84918 - Avignon - France				Contact (sur clinicalTrials)
Polyclinique Bordeaux Nord - 333000 - Bordeaux - France				Contact (sur clinicalTrials)

Critères

Genre

Tous

Nombre d'inclusion

Critère d'inclusion

Inclusion Criteria:

1. 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 these sites:

- breast;

- the chest wall including mastectomy scar and/or skin;

- axillary or internal mammary lymph nodes.

2. 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

3. Negative or microscopically involved margins

4. Female or male aged 18 years or older

5. ECOG performance status 0 or 1

6. Recurrent tumor must be hormone receptor positive: ER+ and/or PgR+ ≥1% by IHC

7. 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

8.-10. Normal hematological, renal, and liver function 11. The patient agrees to make
tumor (diagnostic core biopsy or surgical specimen of ipsilateral isolated locoregional
recurrence) available for submission for central pathology review 12. Patients must
either be planned to initiate, or have already started, endocrine therapy for ipsilateral
isolated locoregional recurrence 13.) Written Informed Consent prior to randomization

Critère de non inclusion

1. Recurrence of any size with direct extension to the chest wall and/or to the skin
(ulceration or skin nodules) not surgically removable

2. 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).

3. Bilateral synchronous or metachronous invasive breast cancer (in situ carcinoma of
the contralateral breast is allowed)

4. Inflammatory breast cancer

5. 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.

6. Previous treatment with palbociclib or any other CDK 4/6 inhibitors

7. 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)

8. 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

9. Pregnant or lactating women; lactation has to stop before randomization

10. Patients with psychiatric illness/social situations that would limit compliance with
study requirements

11. Contraindications or known hypersensitivity to the palbociclib or excipients

12. 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. A history of prior radiation pneumonitis is not considered
an exclusion criterion.

NCT03820830 - A Phase III Open-label, Multicenter, Randomized Trial of Adjuvant Palbociclib in Combination With Endocrine Therapy Versus Endocrine Therapy Alone for Patients With Hormone Receptor Positive / HER2-negative Resected Isolated Locoregional Recurrence of Breast Cancer

Informations générales
Etablissements
Critères
Accès à la fiche NCT

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