Etude : COMPLEEMENT / CLEE011A2404

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Type d'étude
Présentation de l'étude

Nom : CLEE011A2404

Traitement : Néoadjuvant / Adjuvant / Métastasique ou localement avancé

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 25/09/2017
CIM10 - Localisation(s)
Informations principales
Titre : Etude ouverte multicentrique de phase IIIb évaluant la tolérance et l’efficacité de Ribociclib (LEE011) en association avec le Létrozole pour le traitement des femmes préménopausées et ménopausées et des hommes atteints d’un cancer du sein à un stade avancé, avec Récepteurs Hormonaux positifs (RH+), HER2-négatif (HER2-), n’ayant reçu aucun traitement hormonal antérieur au stade avancé de leur maladie

Spécialité : Seins, organes génitaux de la femme
Localisation : C50 - Tumeur maligne du sein
Informations complémentaires
Schéma : Primary Outcome Measures:
- The number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to approximately 36 months ]
AEs, Grade 3/4 AEs & SAEs during treatment with ribociclib + letrozole

Secondary Outcome Measures:
- Time-to-Progression (TTP) [ Time Frame: Up to approximately 36 months ]
Time to progression (TTP) is defined as time from date of start of treatment to the date of event defined as the first documented progression or death due to underlying cancer.

- Overall response rate (ORR) for patients with measurable disease [ Time Frame: Up to approximately 36 months ]
Overall response rate (ORR) is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1.

- Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 36 months ]
Clinical benefit rate (CBR) is defined as the proportion of patients with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. CR, PR and SD are defined according to RECIST 1.1.

- Patient Reported Outcome (PRO) using scores from FACT-B questionaire [ Time Frame: Up to approximately 36 months ]
FACT-B questionnaire will be used to collect patient reported outcome data in this trial. Descriptive statistics will be used to summarize the subscale and overall scores at each scheduled assessment time point. Additionally, change from baseline at the time of each assessment will be summarized. PRO data may be summarized by country/region.

Other Outcome Measures:
- The number of participants with adverse events as a measure of safety and tolerability during Extension Phase [ Time Frame: Up to approximatley 30 months ]
Frequency and severity of AEs and SAEs

- Percentage of patients with clinical benefit during Extension Phase [ Time Frame: Up to approximately 30 months ]
Clinical benefit is assessed by investigator

Phase : IIIb

Stade : NA

Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Male or female advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
- In the case of women, both pre/perimenopausal and postmenopausal patients are allowed to be included in this study; menopausal status is relevant for the requirement of goserelin to be used concomitantly with ribociclib and letrozole.
1. Postmenopausal status is defined either by:
I). Prior bilateral oophorectomy OR ii). Age ≥ 60 OR iii). Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range. If patient is taking tamoxifen or toremifene and age < 60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range.
Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol are needed to ensure menopausal status.

2. Premenopausal status is defined as either:
I). Patient had last menstrual period within the last 12 months, OR ii). If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, OR iii). In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range.

3. Perimenopausal status is define as neither premenopausal nor postmenopausal Note: Throughout this document, perimenopausal and premenopausal status is grouped together and referred as "Premenopausal"

- Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- Patient has adequate bone marrow and organ function as defined by ALL of the following laboratory values (as assessed by local laboratory):
>Absolute neutrophil count ≥ 1.5 × 10^9/L
>Platelets ≥ 100 × 10^9/L
>Hemoglobin ≥ 9.0 g/dL
>Potassium, sodium, calcium corrected for serum albumin and magnesium within normal limits or corrected to within normal limits with supplements before first dose of the study medication
>INR ≤1.5
>Serum creatinine <1.5 mg/dl or creatinine clearance≥50 mL/min
>In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 × ULN. If the patient has liver metastases, ALT and AST should be < 5 × ULN.
>Total serum bilirubin < ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with well-documented Gilbert's Syndrome
- Patient must have a 12-lead ECG with ALL of the following parameters at screening:
>QTcF interval at screening <450 msec (using Fridericia's correction)
>Resting heart rate ≥ 50 bpm

Critères de non-inclusion : - Patient who received any CDK4/6 inhibitor
- Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of metastatic disease is permitted
Informations relatives au promoteur
Promoteur :
Novartis Pharmaceuticals
Type de sponsor : Industriel

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre François BACLESSE - 3 avenue du Général Harris - 14000 CAEN

Investigateur :
Christelle LEVY


Ouverture de l'essai : CLOS

MAJ : 24/01/2018