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Phase 1 / 2 Study of SAR439859 Single Agent and in Combination With Other Anti-cancer Therapies in Postmenopausal Women With Estrogen Receptor Positive Advanced Breast Cancer (AMEERA-1)

Trial Status: Active

Primary Objectives: Dose Escalation: Part A (SAR439859 monotherapy); Part C (combination of SAR439859 with palbociclib); Part F (combination of SAR439859 with alpelisib) - To determine the maximum tolerated dose (MTD) and recommended dose (RD) of SAR439859 based on the dose-limiting toxicity observance in monotherapy (Part A), in combination with palbociclib (Part C) and in combination with alpelisib (Part F) Dose Expansion: Part B (SAR439859 monotherapy): - To assess antitumor activity by Objective Response Rate (ORR) at the SAR439859 recommended dose in monotherapy Dose Expansion: Part D (combination of SAR439859 with palbociclib) and Part G (combination of SAR439859 with alpelisib): - Overall safety profile of SAR439859 in combination with palbociclib and alpelisib Midazolam Drug-Drug Interaction Sub-Study: Part E - To assess the effect of SAR439859 on CYP3A enzyme activity using midazolam as a probe Secondary Objectives: - Overall safety profile of SAR439859 as monotherapy (Parts A, B, E), in combination with palbociclib (Part C) or in combination with alpelisib (Part F) - Pharmacokinetic (PK) profile of SAR439859 as monotherapy (Parts A, B, E), in combination with palbociclib (Parts C, D, E), in combination with alpelisib (Parts F, G, E), and PK of palbociclib (Parts C, D) and alpelisib (Parts F, G) alone and / or with SAR439859 - Antitumor activity of SAR439859 as monotherapy (Part A, E), in combinations with palbociclib (Part C, D, E) or alpelisib (F, G, E), and Clinical Benefit Rate (CBR: Complete Response [CR], Partial Response [PR] and Stable Disease [SD] ≥24 weeks) in Parts A, B, C, D, E, F, G - ORR and CBR in Parts B, D, E and G according to the estrogen receptor 1 (ESR1) gene mutational status (mutant and wild type) at baseline and in treatment - Time to first tumor response (CR,PR) (Part B, D, G) - Residual estrogen receptor (ER) availability with [(18)F] Fluoroestradiol Positron Emission Tomography (FES PET) scan (Part A) - To assess potential induction / inhibition effect of SAR439859 on CYP3A (Part A, B, E)

Inclusion Criteria

  • Inclusion criteria: Parts A, B, C, D, E, F and G: - Patients must be postmenopausal women - Histological diagnosis of breast adenocarcinoma - Locally advanced or metastatic disease - Either primary tumor or any metastatic site to be positive for Estrogen Receptors (ER+) and negative for HER2 (HER2-) receptor - Patients previously treated with endocrine therapy for advanced disease: at least 6 months exposure to endocrine therapy (Patients with early relapse while on adjuvant endocrine therapy that was initiated ≥24 months ago, or who relapsed < 12 months after completion of adjuvant endocrine therapy are eligible); in Part D, no more than 2 prior lines of endocrine therapy are allowed; in Parts F and G, no more than 2 prior lines of endocrine therapy for advanced disease are allowed including 1 line that may have been combined with a CDK4/6 inhibitor; and, prior use of a CDK4/6 inhibitor is not mandated - Patients previously treated with chemotherapy for advanced disease: no more than 3 prior chemotherapeutic regimens in Part A, and no more than 1 prior chemotherapeutic regimen in Parts B, C, D, E and F (including Antibody Drug Conjugates) - Measurable lesion Exclusion criteria: - Medical history or ongoing gastrointestinal disorders that could affect absorption of SAR439859 and/or palbociclib (including difficulties with swallowing capsules) - Patient with any other cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or any other cancer from which the patient has been disease free for >3 years) - Patients with known brain metastases - Treatment with anticancer agents (including investigational drugs) less than 2 weeks before first study treatment starts (less than 4 weeks if the anticancer agents were antibodies) - Prior treatment with another selective ER down-regulator (SERD) (except fulvestrant) with a washout of at least 6 weeks prior to the first study drug administration - Inadequate hematological and biochemical lab tests - Patients with Gilbert disease - Treatment with human immunodeficiency virus (HIV)-antiviral, antifungal and antioxidant agents less than 2 weeks before study treatment starts - Treatment with strong and moderate cytochrome P450 (CYP) 3A or CYP2C8 inducers within 2 weeks before first study treatment - Treatment with strong CYP3A inhibitors within 2 weeks before first study treatment starts - More than one prior cyclin-dependent kinase (CDK) 4/6 inhibitor based therapy Part A only: - Patients with liver metastases only Part D only: - Prior therapy with any selective CDK4/6 inhibitor, phosphoinositide 3-kinase (PI3K) inhibitors, mammalian target of rapamycin (mTOR) inhibitors and AKT inhibitors Part E only: - Treatment with any CYP3A inducer or CYP3A inhibitors within 2 weeks before midazolam administration - Any contraindications to midazolam (in accordance with the applicable label) - Use of any herbal medicines 1 week, and grapefruit juice for 72 hours before midazolam administration and up to the end of PK sampling following the last midazolam administration - Patients older than 60 years The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Colorado

Aurora
University of Colorado Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: ACTIVE
Massachusetts General Hospital Cancer Center
Status: ACTIVE

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: ACTIVE

South Carolina

Charleston
Medical University of South Carolina
Status: COMPLETED

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Marcella West Aguilar
Phone: 214-648-1479

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE

Duration of the study, per patient, will include eligibility period (screening period) of up to 4 weeks (28 days), treatment period (at least 1 cycle [28 days] of study treatment), and end of treatment (EOT) visit after the last study treatment administration (i.e. at least 30 days post last treatment or until the patient receives another anticancer therapy, whichever is earlier). The expected enrollment period is approximately 42 months.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Sanofi Aventis

  • Primary ID TED14856
  • Secondary IDs NCI-2017-01882, U1111-1189-4896, 2017-000690-36
  • Clinicaltrials.gov ID NCT03284957