Description:
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).
Title
- Brief Title: Evaluation of Orally Administered Amcenestrant (SAR439859) in Japanese Postmenopausal Patients With Advanced Breast Cancer
- Official Title: A Phase 1 Study for the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics Evaluation of SAR439859, Administered Orally as Monotherapy in Japanese Postmenopausal Women With Estrogen Receptor-Positive And Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer (AMEERA-2)
Clinical Trial IDs
- ORG STUDY ID:
TED15954
- SECONDARY ID:
U1111-1217-2758
- NCT ID:
NCT03816839
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Amcenestrant (SAR439859) | | SAR439859 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| SAR439859 | Experimental | administered orally once daily or twice daily as monotherapy in fasted or fed state | |
Eligibility Criteria
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 20 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Investigational medicinal product (IMP)-related dose limiting toxicities (DLTs) |
| Time Frame: | Day 1 to Day 28 |
| Safety Issue: | |
| Description: | Incidence rate of study treatment-related DLTs at Cycle 1 |
Secondary Outcome Measures
| Measure: | Safety: Adverse Events (AEs) |
| Time Frame: | Up to 30 days after administration of study treatment |
| Safety Issue: | |
| Description: | Number of adverse events related to study therapy |
| Measure: | Assessment of Pharmacokinetic parameter of SAR439859: tlag |
| Time Frame: | Day 1 and Day 22 of Cycle 1 (28 days) |
| Safety Issue: | |
| Description: | Lag time, interval between administration time and the sampling time preceding the first concentration above the lower limit of quantification |
| Measure: | Assessment of Pharmacokinetic parameter of SAR439859: tmax |
| Time Frame: | Day 1 and Day 22 of Cycle 1 (28 days) |
| Safety Issue: | |
| Description: | First time to reach Cmax |
| Measure: | Assessment of Pharmacokinetic parameter of SAR439859: Cmax |
| Time Frame: | Day 1 and Day 22 of Cycle 1 (28 days) |
| Safety Issue: | |
| Description: | Maximum concentration observed |
| Measure: | Assessment of Pharmacokinetic parameter of SAR439859: AUC0-24h or AUC0-10h and/or AUC0-12h |
| Time Frame: | Day 1 and Day 22 of Cycle 1 (28 days) |
| Safety Issue: | |
| Description: | Area under the plasma concentration versus time curve over the dosing interval (24 hours, 10 hours or 12 hours) |
| Measure: | Assessment of Pharmacokinetic parameter of SAR439859: Ctrough |
| Time Frame: | Day 1, Day 8, Day 15 and Day 22 of Cycle 1 (28 days) and Day 1 of Cycle 2 |
| Safety Issue: | |
| Description: | Plasma concentration observed just before treatment administration during repeated dosing |
| Measure: | Assessment of antitumor activity: Objective response rate (ORR) |
| Time Frame: | 64 weeks |
| Safety Issue: | |
| Description: | Objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) |
| Measure: | Assessment of antitumor activity: Clinical benefit rate (CBR) |
| Time Frame: | 64 weeks |
| Safety Issue: | |
| Description: | Clinical benefit rate is (CR [complete response] +PR [partial response] +SD [stable disease] ≥24 weeks) as per RECIST 1.1 |
| Measure: | Assessment of antitumor activity: Duration of response |
| Time Frame: | 64 weeks |
| Safety Issue: | |
| Description: | Response duration defined as the time from initial response to the first documented tumor progression |
| Measure: | Assessment of antitumor activity: Non-progression rate |
| Time Frame: | 64 weeks |
| Safety Issue: | |
| Description: | Non-progression rate at 24 weeks (percentage of participants without progression at 24 weeks) |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Sanofi |
Last Updated
July 21, 2021
