Phase 2 window study of SAR439859 versus letrozole in ER+, HER2- preoperative post-menopausal primary breast cancer
- Conditions
- Breast CancerMedDRA version: 20.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002015-26-IT
- Lead Sponsor
- SANOFI-AVENTIS RECHERCHE E DEVELOPPEMENT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 160
- Histological or cytological proven diagnosis of invasive breast adenocarcinoma
- Localized breast cancer eligible for upfront breast conservative surgery or upfront mastectomy: Stage I, 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:
-Spontaneous cessation of menses >12 months;
-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 post bilateral ovarian ablation through pelvic radiotherapy.
-Breast tumor size of at least 10 mm in greatest dimension 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
- 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), CYP2C8 inducers or drugs that have the potential to inhibit UGT within 2 weeks before first study treatment administration or 5 elimination halflives whichever is longest
-Ongoing treatment with drugs that are sensitive substrates of Pglycoprotein (P-gp)
-Use of any investigational agent within 4 weeks prior to randomization
-Recent use of hormone replacement therapy (last dose -Prior anti-cancer treatment is not allowed unless it was completed at least 1 year prior to inclusion into this trial
-Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments)
-Inadequate hematological or renal function
-Prothrombin time/international normalized ratio (INR) >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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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<br>-To assess estrogen receptor (ER) degradation in biopsies in participants in the three treatment arms<br>-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 Outcome Measures
Name Time Method 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<br>2. ER Expression: Change in ER expression after a 14-day treatment period compared to baseline<br>3. Adverse Events (AEs)/Serious Adverse Events (SAEs): Percentage of participants with AEs/SAEs<br>4. Clinical Laboratory Test Abnormalities: Percentage of participants with clinical laboratory test abnormalities.;Timepoint(s) of evaluation of this end point: 1. Baseline and Day 15<br>2. Baseline and Day 15<br>3. Up to approximately Day 44<br>4. Up to Day 14.