Clinical trial NCT04191382: Phase 2 Window Study of SAR439859 (Amcenestrant) Versus Letrozole in Post-menopausal Patients With ER+, HER2- Pre-operative Post-menopausal Primary Breast Cancer
Official title: Phase 2 Window Study of Two Dose Levels of Amcenestrant [SAR439859] (SERD) Versus Letrozole in Newly Diagnosed Pre-operative Post-menopausal Patients With ER Positive, HER2 Negative Primary Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-12-09
Enrollment: 105
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To determine whether amcenestrant given at 2 different doses improved the antiproliferative activity when compared to letrozole.

Secondary Objectives:

* To assess the proportion of participants with a relative decrease from Baseline in percentage of positive tumor cells tested by immunohistochemistry greater than or equal to (\>=) 50 percent (%) (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.

Detailed description: Duration of the study, per participant, would include screening period of up to 14 days before randomization, treatment period of 14 days and post-treatment safety follow-up period of 30±7 days after last investigational medicinal product (IMP) intake.

Eligibility criteria: Inclusion criteria :

* 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 (excluded 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 greater than (\>) 12 months.
* or who had received hormonal replacement therapy but had discontinued the treatment and had follicle stimulating hormone (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 millimeters (mm) in greatest dimension measured by ultrasound.
* Primary tumor had to 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.

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.
* Participants with known active hepatitis A, B, C infection; or hepatic cirrhosis.
* 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 had been disease free for \>3 years were allowed.
* Evidence of metastatic spread by standard assessment according to local practice.
* Treatment with strong Cytochrome P450 3A (CYP3A) inducers or drugs that had the potential to inhibit uridine diphosphate glucuronosyltransferase (UGT) within 2 weeks before first study treatment administration or 5 elimination half-lives whichever was longest.
* Treatment with drugs that were sensitive substrates of P-glycoprotein (P-gp) or of breast cancer resistance protein (BCRP) within 2 weeks before first study treatment administration or 5 elimination half-lives whichever was longer.
* Use of any investigational agent within 4 weeks prior to randomization.
* Recent use of hormone replacement therapy (last dose less than or equal to \[\<=\] 30 days prior to randomization).
* Prior anti-cancer treatment was not allowed unless it was then 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 \* upper limit of normal (ULN) or outside therapeutic range if received anticoagulation that would have had affected the prothrombin time/INR.
* Any of the following abnormal liver function test results: Aspartate aminotransferase \>1.5 \* ULN; Alanine aminotransferase \>1.5 \* ULN; Total bilirubin \>1.5 \* ULN.
* Participants were 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.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Percent Change From Baseline in Ki67 Level at Day 15
timeFrame: Baseline, Day 15
Secondary outcomes:
measure: Percentage of Participants With Percent Change From Baseline in Ki67 Greater Than or Equal to (>=) 50 Percent at Day 15
timeFrame: Baseline, Day 15
measure: Change From Baseline in Estrogen Receptor (ER) Expression as Measured by H-Score at Day 15
timeFrame: Baseline, Day 15
measure: Number of Participants With Abnormalities: Hematological Parameters
timeFrame: From first dose of study drug up to Day 14
measure: Number of Participants With Abnormalities: Clinical Chemistry
timeFrame: From first dose of study drug up to Day 14
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Investigational Site Number 8400014
state: Arizona
city: Los Angeles
country: United States
facility: Investigational Site Number 8400010
state: California
city: Fort Wayne
country: United States
facility: Investigational Site Number 8400018
state: Indiana
city: Lincoln
country: United States
facility: Investigational Site Number 8400005
state: Nebraska
city: Winston-Salem
country: United States
facility: Investigational Site Number 8400016
state: North Carolina
city: Tacoma
country: United States
facility: Investigational Site Number 8400012
state: Washington
city: Leuven
country: Belgium
facility: Investigational Site Number 0560001
city: Namur
country: Belgium
facility: Investigational Site Number 0560002
city: Nantes
country: France
facility: Investigational Site Number 2500001
city: Paris
country: France
facility: Investigational Site Number 2500004
city: Saint Cloud
country: France
facility: Investigational Site Number 2500002
city: Toulouse Cedex 9
country: France
facility: Investigational Site Number 2500003
city: Meldola
country: Italy
facility: Investigational Site Number 3800004
city: Milano
country: Italy
facility: Investigational Site Number 3800002
city: Milano
country: Italy
facility: Investigational Site Number 3800001
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 3920002
city: Sapporo-Shi
country: Japan
facility: Investigational Site Number 3920003
city: Yokohama-Shi
country: Japan
facility: Investigational Site Number 3920001
city: Hato Rey
country: Puerto Rico
facility: Investigational Site Number 8400007
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430006
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430004
city: Saint -Petersburg
country: Russian Federation
facility: Investigational Site Number 6430002
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430003
city: St.Petersburg
country: Russian Federation
facility: Investigational Site Number 6430007
city: Barcelona
country: Spain
facility: Investigational Site Number 7240005
city: Córdoba
country: Spain
facility: Investigational Site Number 7240003
city: Madrid
country: Spain
facility: Investigational Site Number 7240001
city: Valencia / Valencia
country: Spain
facility: Investigational Site Number 7240002
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 8040004
city: Uzhgorod
country: Ukraine
facility: Investigational Site Number 8040001
city: Vinnytsia
country: Ukraine
facility: Investigational Site Number 8040002
city: Zaporizhzhya
country: Ukraine
facility: Investigational Site Number 8040005
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: