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
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : APPALACHES

Nom :

Traitement : Adjuvant / Métastasique ou localement avancé

Type d'étude : Ciblage moléculaire / Innovation thérapeutique

Dernière MÀJ : 19/09/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Phase II study of Adjuvant PALbociclib as an Alternative to CHemotherapy in Elderly patientS with high-risk ER+/HER2- early breast cancer

Spécialité : Seins, organes génitaux de la femme
Localisation : C50 - Tumeur maligne du sein
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : This is a two-arm open-label multi-center randomized (2:1) non-comparative phase II study in elderly patients with stage II/III, ER+, HER2- early breast cancer for whom treatment with chemotherapy is indicated.

Patients will be randomized with a 2:1 allocation rate to the following treatment arm:
- experimental palbociclib arm: Standard adjuvant endocrine therapy for a duration of at least 5 years + palbociclib for a total duration of up to 2 years.
- control chemotherapy arm: adjuvant chemotherapy (4 cycles of docetaxel/doxorubicin/epirubicin-cyclophosphamide; or of weekly paclitaxel D1, D8, and D15 q3w if a 3 weekly schedule is not desired), followed by standard adjuvant endocrine therapy for a duration of at least 5 years.

Main objective of the trial:
The primary objective of this trial is to assess the efficacy of the combination of at least 5 year endocrine therapy and 2 year-palbociclib as adjuvant systemic treatment instead of adjuvant chemotherapy followed by endocrine therapy in older patients with stage II-III ER+/HER2- early breast cancer.

Secondary objectives of the trial:
- To evaluate the efficacy with respect to different time-to-event endpoints (distant recurrence-free interval (DRFI), breast cancer specific survival (BCSS), OS) at 3, 6 and 10 years in both arms
- To evaluate toxicity in both arms
- To evaluate the treatment discontinuation and dose reduction rates in both arms
- To assess the reasons for treatment discontinuation
- To evaluate completion of oral therapy in the experimental arm
- To assess the evolution of Health-Related Quality of Life (HRQoL) in both arms
- To assess the evolution, prognostic and predictive effects of geriatric assessment in both arms

Phase : II

Stade : Localisé à Localement avancé

1
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
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 :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Oscar Lambret - 3 Rue Frédéric Combemale - 59000 LILLE

Investigateur :
Docteur Audrey MAILLIEZ

TEC / ARC / IDE :
Unité Intégrée de Recherche Clinique
investigation@
o-lambret.fr
03.20.29.59.35

Ouverture de l'essai : OUVERT

MAJ : 18/09/2019