Breast Cancer
Conditions
Brief summary
Primary Objective: To assess the incidence rate of dose-limiting toxicity and to confirm the recommended dose as well as the maximum tolerated dose of SAR439859 administered as monotherapy to Japanese postmenopausal women with estrogen receptor positive and human epidermal growth factor receptor 2-negative advanced breast cancer. Secondary Objective: * To characterize the overall safety profile of SAR439859 administered as monotherapy. * To characterize the pharmacokinetic profile of SAR439859 administered as monotherapy. * To evaluate the antitumor activity of SAR439859 administered as monotherapy and the clinical benefit rate (complete response, partial response and stable disease ≥ 24 weeks).
Detailed description
The duration of the study for an individual participant will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of at least 1 cycle (28 days) of study treatment, and an End of Treatment (EOT) visit at least 30 days (or until the participant receives another anticancer therapy, whichever is earlier) following the last administration of study treatment. Study treatment may continue until precluded by unacceptable toxicity, disease progression, or upon participant's request.
Interventions
Pharmaceutical form: Capsules Route of administration: Oral
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Participants must be postmenopausal women. * Breast adenocarcinoma patients with locally advanced not amenable to radiation or surgery, inoperable and/or metastatic disease. * Either the primary or any metastatic site must be positive for estrogen receptor (ER) (\>1% staining by immunohistochemistry). * Either the primary tumor or any metastatic site must be human epidermal growth factor receptor 2 non-overexpressing. * Patients with at least 6 months of prior endocrine therapy.
Exclusion criteria
* Eastern Cooperative Oncology Group Performance Status (ECOG) ≥2. * Significant concomitant illness that would adversely affect participation in the study. * Patients with a life expectancy less than 3 months. * Patient not suitable for participation, whatever the reason. * Major surgery within 4 weeks prior to first study treatment administration. * Treatment with strong and moderate cytochrome P450 3A inhibitors/inducers. * Patients with known endometrial disorders, uterine bleeding or ovarian cysts. * Treatment with anticancer less than 2 weeks before first study treatment. * Prior treatment with selective estrogen receptor down (SERD)-regulator (except fulvestrant for which a washout of at least 6 weeks is required). * Inadequate hematological function. * Inadequate renal function with serum creatinine ≥1.5 x upper limit of normal (ULN). * Liver function: aspartate aminotransferase \>3 x ULN, or alanine aminotransferase \>3 x ULN. Total bilirubin \>1.5 x ULN. * Non-resolution of any prior treatment related toxicity to \<Grade 2, except for alopecia The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigational medicinal product (IMP)-related dose limiting toxicities (DLTs) | Day 1 to Day 28 | Incidence rate of study treatment-related DLTs at Cycle 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Pharmacokinetic parameter of SAR439859: tlag | Day 1 and Day 22 of Cycle 1 (28 days) | Lag time, interval between administration time and the sampling time preceding the first concentration above the lower limit of quantification |
| Assessment of Pharmacokinetic parameter of SAR439859: tmax | Day 1 and Day 22 of Cycle 1 (28 days) | First time to reach Cmax |
| Assessment of Pharmacokinetic parameter of SAR439859: Cmax | Day 1 and Day 22 of Cycle 1 (28 days) | Maximum concentration observed |
| Assessment of Pharmacokinetic parameter of SAR439859: AUC0-24h or AUC0-10h and/or AUC0-12h | Day 1 and Day 22 of Cycle 1 (28 days) | Area under the plasma concentration versus time curve over the dosing interval (24 hours, 10 hours or 12 hours) |
| Safety: Adverse Events (AEs) | Up to 30 days after administration of study treatment | Number of adverse events related to study therapy |
| Assessment of antitumor activity: Objective response rate (ORR) | 64 weeks | Objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) |
| Assessment of antitumor activity: Clinical benefit rate (CBR) | 64 weeks | Clinical benefit rate is (CR \[complete response\] +PR \[partial response\] +SD \[stable disease\] ≥24 weeks) as per RECIST 1.1 |
| Assessment of antitumor activity: Duration of response | 64 weeks | Response duration defined as the time from initial response to the first documented tumor progression |
| Assessment of antitumor activity: Non-progression rate | 64 weeks | Non-progression rate at 24 weeks (percentage of participants without progression at 24 weeks) |
| Assessment of Pharmacokinetic parameter of SAR439859: Ctrough | Day 1, Day 8, Day 15 and Day 22 of Cycle 1 (28 days) and Day 1 of Cycle 2 | Plasma concentration observed just before treatment administration during repeated dosing |
Countries
Japan
Outcome results
None listed