Etude : APPALACHES /



ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.


Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : APPALACHES

Situation thérapeutique : Adjuvant

Traitement : Chimiothérapie / Thérapie ciblée

Cadre réglementaire : RIPH1

Dernière MÀJ : 14/01/2022
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Étude de phase II portant sur le palbociclib comme traitement adjuvant alternatif à la chimiothérapie en cas de cancer du sein de stade précoce ER+/HER2-négatif à haut risque chez des patients âgés

Spécialité : Seins, organes génitaux de la femme
Localisation : C50 - Tumeur maligne du sein
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : L'objectif principal de cet essai est d'évaluer l'efficacité de l'association d'une thérapie endocrinienne d'au moins 5 ans et de 2 ans de palbociclib comme traitement systémique adjuvant au lieu d'une chimiothérapie adjuvante suivie d'un traitement endocrinien chez des patients âgés atteints de stade II-III ER + / HER2- cancer du sein précoce.

Il s'agit d'une étude de phase II non comparative multicentrique ouverte à deux bras, randomisée (2: 1) chez des patientes âgées atteintes d'un cancer du sein précoce de stade II / III, ER +, HER2- pour lesquelles un traitement par chimiothérapie est indiqué.

Les patients seront randomisés avec un taux d'attribution de 2: 1 au bras de traitement suivant:

bras palbociclib expérimental: traitement endocrinien adjuvant standard pour une durée d'au moins 5 ans + palbociclib pour une durée totale allant jusqu'à 2 ans.
bras de chimiothérapie témoin: chimiothérapie adjuvante (4 cycles de docétaxel / doxorubicine / épirubicine-cyclophosphamide; ou de paclitaxel hebdomadaire J1, J8 et J15 toutes les 3 semaines si un schéma de 3 semaines n'est pas souhaité), suivis d'un traitement endocrinien adjuvant standard pendant une durée d'au au moins 5 ans.
Le critère d'évaluation principal de l'étude est le taux de D-RFI à 3 ans dans le bras expérimental.

Phase : II

Stade : Localisé à Localement avancé

NA
Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Women or men with stage II or stage III, early invasive breast cancer according to the UICC 8th edition for TNM classification
- Histologically confirmed ER+ , HER-2 negative, early invasive breast cancer based on results of local pathology. Testing may be performed on
diagnostic core biopsy or resection specimen.
- In patients with multicentric, multifocal and/or bilateral breast cancer, all histopathologically examined invasive tumors must meet pathologic
criteria regarding ER and HER2-status described above.
- Adjuvant chemotherapy indicated and feasible according to treating physician and patient, based on standard clinicopathological parameters
(tumor size, lymph node involvement, general health status, proliferation marker, patient wish) and gene expression profile if available.
- Adjuvant chemotherapy with both anthracycline and taxanes (in combination or in sequence) considered not indicated or not feasible according to treating physician.
- Age ≥70 years
- WHO Performance status 0-2
- Completed G8 geriatric assessment within 3 weeks of randomization.
- Participation in translational research is mandatory and therefore patient must consent for it. Patient should allow sequential sampling of blood during the course of the trial
- Patient must have undergone breast +/- axillary surgery with curative intent for the current malignancy ≤8 weeks before randomization. The
final primary tumor surgical specimen must have R0 margins free from tumor.
- Patients must have sufficient resolution of any surgical side effects from the last surgery per physician assessment, with no active wound
healing complications at the time of randomization.
- Incentive to undergo adjuvant radiation therapy when indicated per local institutional guidelines.
Note: For patients in the palbociclib arm, radiation therapy when indicated has to start ≤9 weeks after last surgery. The endocrine therapy can be initiated during or after the radiation therapy but not later than 3 weeks after the last radiotherapy. Palbociclib has to start ≤3 weeks after the last radiotherapy. When radiation therapy is not indicated, endocrine
therapy and palbociclib have to be initiated ≤9 weeks after last surgery.
Note: For patients in the chemotherapy arm, chemotherapy has to be the first adjuvant treatment and has to start ≤9 weeks after the last surgery.
When radiation therapy is indicated, this treatment has to start ≤6 weeks after the last chemotherapy administration. Adjuvant endocrine therapy can be initiated during or after the radiation therapy but not
later than 3 weeks after the last radiotherapy. When radiation therapy is not indicated, endocrine therapy has to be initiated ≤6 weeks after last
chemotherapy administration.
- Adequate baseline organ function, evidenced by the following laboratory results within 3 weeks of randomization:
- Hemoglobin ≥ 9 g/dL
- Absolute neutrophil count (ANC) ≥ 1500/mm3
- Platelet count ≥ 100,000/mm3
- Total bilirubin ≤ 1.5 upper limit of normal (ULN), or total bilirubin ≤ 3.0 × ULN in patients with documented Gilbert's Syndrome.
- Glomerular Filtration Rate (GFR) ≥ 30 ml/min according to MDRD formula or CKD-EPI formula or Cockcroft and Gault formula
- SGOT (AST), SGPT (ALT) and alkaline phosphatase ≤ 2.5 × ULN
- Patients must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption.
- For men participating in the trial:
• As fertility may be affected permanently with protocol treatment, we advise offering to patient sperm preservation prior to treatment.
• Patient with partner of childbearing / reproductive potential should use two birth control methods, as defined by the investigator, from the time of signing the informed consent form , and throughout the entire study and for 6 months after the last dose of chemotherapies or 3 months and half (14 weeks) after last dose of palbociclib. Two (2) of the
following barrier methods in combination are allowed during the study.
It is strongly recommended that at least one of these two methods be highly effective. A highly effective contraceptive method is one that has
a failure rate of less than 1% and does not interfere with the proposed investigations.
Highly effective methods: Intra-uterine devices (IUD) or Hormonal (birth control pills/oral contraceptives, injectable contraceptives, contraceptive patches, or contraceptive implants)
Other effective methods (barrier methods): Latex condom or Diaphragm with spermicide; Cervical cap; Sponge
If one of the highly effective methods cannot be used, using two other effective methods at the same time is required.
Birth control methods as directed above must be used unless patient completely avoid having heterosexual intercourse.
Note: for sexual abstinence: occasional abstinence, the rhythm method and the withdrawal method are not acceptable methods of contraception.
- Signed, written informed consent.

Critères de non-inclusion : - Evidence of macroscopic distant metastases, investigated according to local institutional guidelines.
- Previous history of invasive breast cancer
- Patients who received treatment with live vaccines within 30 days prior the first dose of study medication.
- Systemic anticancer therapy prior to the breast cancer surgery
- Prior therapy with any CDK4/6 inhibitor
- Concurrent investigational agent within 28 days of randomization
- Concomitant anticancer treatment with the exception of bone
antiresorptive agents or LHRH agonists in male patients treated with an aromatase-inhibitor
- History of allergic reactions attributed to compounds of chemical or biological composition similar to palbociclib or to chemotherapy components
- Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
- Medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including known HIV, active hepatitis B and/or hepatitis C infection), symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or uncontrolled diabetes.
Note: For patients for whom doxorubicin or epirubicin is planned, an adequate baseline cardiac function (left ventricular ejection fraction ≥
50%) should have been proven no more than 1 year before treatment start.
- 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
- Other malignancy within the last 5 years except: adequately treated non-metastatic non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ of the breast.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03609047
Promoteur :
European Organisation for Research and Treatment of Cancer - EORTC
Type de sponsor : Institutionnel
00000 HORS FRANCE

Coordonnateur :
EORTC
1745@eortc.org
+3227741611
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Henri Becquerel - Rue d'Amiens CS 11516 - Cedex 1 - 76000 ROUEN

Investigateur :
Dr Olivier RIGAL

TEC / ARC / IDE :
Lorena MASSELINE
lorena.masseline@
chb.unicancer.fr
0232082961

Statut de l'essai : OUVERT

MAJ : 29/01/2021