Cancer MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Histological or cytological proven diagnosis of invasive breast adenocarcinoma -Localized breast cancer eligible for immediate breast conservative surgery: Stage II or operable Stage III (excludes T4) as defined in American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th edition 2017 -Postmenopausal women as defined by one of the following: -Age =60 years -Age 12 months; or with cessation of menses of duration =12 months or secondary to hysterectomy and have follicle stimulating hormone (FSH) level in the postmenopausal range; or who have received hormonal replacement therapy but have discontinued this treatment and have FSH level in the postmenopausal range; or with status post bilateral surgical oophorectomy; or postbilateral ovarian ablation through pelvic radiotherapy; or are premenopausal women on a gonadotropin-releasing hormone (GnRH) analog for at least 4 weeks (to be continued during study treatment) -Breast tumor size of at least 10 mm in short axis measured by ultrasound -Primary tumor must be positive for Estrogen Receptors (ER+) and negative for HER2 (HER2-) receptor by immunohistochemistry -Ki67 level of at least 15% at diagnosis from immunohistochemistry of the tumor -Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of SAR439859 or letrozole; Participants unable to swallow normally and to take capsules or tablets -Participant with any other cancer; adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or any other cancer from which the participant has been disease free for >3 years are allowed -Evidence of metastatic spread by standard assessment according to local practice -Treatment with strong or moderate Cytochrome P450 3A (CYP3A) or CYP2C8 inducers within 2 weeks before first study treatment administration or 5 elimination half-lives whichever is longest -Ongoing treatment with drugs that are sensitive substrates of P-glycoprotein (P-gp) -Use of any investigational agent within 4 weeks prior to randomization -Currently receiving (and unwilling to discontinue) hormone replacement therapy (last dose 1.5 x ULN) or outside therapeutic range if receiving anticoagulation that would affect the prothrombin time/INR -Any of the following abnormal liver function test results: Aspartate aminotransferase >1.5 x upper limit of normal (ULN); Alanine aminotransferase >1.5 x ULN; Total bilirubin >1.5 x ULN -Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals -Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether SAR439859 given at 2 different doses improves the antiproliferative activity when compared to letrozole;Secondary Objective: -To assess the proportion of participants with a relative decrease from baseline in percentage of positive tumor cells tested by immunohistochemistry =50% (Ki67=50%) in the three treatment arms -To assess estrogen receptor (ER) degradation in biopsies in participants in the three treatment arms -To assess safety in the three treatment arms;Primary end point(s): Ki67: Change in Ki67 (percentage of positive tumor cells tested by immunohistochemistry) after a 14-day treatment period compared to baseline assessed by central reading;Timepoint(s) of evaluation of this end point: Baseline and Day 15 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. Baseline and Day 15 2. Baseline and Day 15 3. Up to approximately Day 44 4. Up to Day 14;Secondary end point(s): 1. Ki67=50%: Proportion of participants with relative change from baseline in Ki67=50% after a 14-day treatment period compared to baseline 2. ER Expression: Change in ER expression after a 14-day treatment period compared to baseline 3. Adverse Events (AEs)/Serious Adverse Events (SAEs): Percentage of participants with AEs/SAEs 4. Clinical Laboratory Test Abnormalities: Percentage of participants with clinical laboratory test abnormalities | — |
Countries
Belgium, France, Italy, Russian Federation, Spain, United States
Contacts
Public ContactUnidad de Estudios Clínicos
sanofi-aventis, s.a.
Outcome results
None listed