E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether SAR439859 given at 2 different doses improves the antiproliferative activity when compared to letrozole |
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E.2.2 | Secondary objectives of the trial |
-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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 <60 years with: spontaneous cessation of menses >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 |
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E.4 | Principal 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 <14 days prior to randomization) -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 |
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
France |
Italy |
Russian Federation |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |