Clinical trial NCT03816839: Evaluation of Orally Administered Amcenestrant (SAR439859) in Japanese Postmenopausal Patients With Advanced Breast Cancer (AMEERA-2)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Breast Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-01-25
Enrollment: 10
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Investigational medicinal product (IMP)-related dose limiting toxicities (DLTs)
timeFrame: Day 1 to Day 28
Secondary outcomes:
measure: Safety: Adverse Events (AEs)
timeFrame: Up to 30 days after administration of study treatment
measure: Assessment of Pharmacokinetic parameter of SAR439859: tlag
timeFrame: Day 1 and Day 22 of Cycle 1 (28 days)
measure: Assessment of Pharmacokinetic parameter of SAR439859: tmax
timeFrame: Day 1 and Day 22 of Cycle 1 (28 days)
measure: Assessment of Pharmacokinetic parameter of SAR439859: Cmax
timeFrame: Day 1 and Day 22 of Cycle 1 (28 days)
measure: Assessment of Pharmacokinetic parameter of SAR439859: AUC0-24h or AUC0-10h and/or AUC0-12h
timeFrame: Day 1 and Day 22 of Cycle 1 (28 days)
measure: Assessment of Pharmacokinetic parameter of SAR439859: Ctrough
timeFrame: Day 1, Day 8, Day 15 and Day 22 of Cycle 1 (28 days) and Day 1 of Cycle 2
measure: Assessment of antitumor activity: Objective response rate (ORR)
timeFrame: 64 weeks
measure: Assessment of antitumor activity: Clinical benefit rate (CBR)
timeFrame: 64 weeks
measure: Assessment of antitumor activity: Duration of response
timeFrame: 64 weeks
measure: Assessment of antitumor activity: Non-progression rate
timeFrame: 64 weeks
Other outcomes:
Locations:
city: Nagoya-shi
country: Japan
facility: Investigational Site Number : 3920003
state: Aichi
city: Kashiwa-shi
country: Japan
facility: Investigational Site Number : 3920001
state: Chiba
city: Chuo-ku
country: Japan
facility: Investigational Site Number : 3920002
state: Tokyo
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Tamura K, Mukohara T, Yonemori K, Kawabata Y, Nicolas X, Tanaka T, Iwata H. Phase 1 study of oral selective estrogen receptor degrader (SERD) amcenestrant (SAR439859), in Japanese women with ER-positive and HER2-negative advanced breast cancer (AMEERA-2). Breast Cancer. 2023 May;30(3):506-517. doi: 10.1007/s12282-023-01443-8. Epub 2023 Mar 29.