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Protocol # 17-371

Status

Recruiting

Description

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)

Condition

  • Breast Cancer

Interventions

  • SAR439859
  • palbociclib
  • midazolam
  • alpelisib

Phase

Phase 1/Phase 2

Study Type

Interventional

Further Study Details

Primary Outcome:

  • Part A : To determine the RD of SAR439859
  • Part C : To determine the RD of SAR439859 in combination with palbociclib
  • Part F: To determine the RD of SAR439859 in combination with alpelisib
  • Part B : to evaluate the ORR of SAR439859
  • Part D, G: Adverse Events
  • Part E: AUClast and AUC of midazolam

Secondary Outcome:

  • Part A, B, C, E and F: Adverse Events
  • ORR
  • Time to First Response (TTR)
  • Clinical Benefit Rate (CBR)
  • Duration of response
  • tlag of SAR439859 after single dose (Part A, B, C, D)
  • tmax of SAR439859 after single dose (Part A, B, C, D)
  • Cmax of SAR439859 after single dose (Part A, B, C, D)
  • AUC0-24 of SAR439859 after single dose (Part A, B, C, D)
  • tmax of SAR439859 after repeated dose administration (Part A, B, C, D)
  • Cmax of SAR439859 after repeated dose administration (Part A, B, C, D)
  • AUC0-24 of SAR439859 after repeated dose administration (Part A, B, C, D)
  • Ctrough of SAR439859 during repeated dose administration (Part A, B, C, D)
  • tmax of palbociclib after single dose (Part C, D)
  • Cmax of palbociclib after single dose (Part C, D)
  • AUC0-24 of palbociclib after single dose (Part C, D)
  • tmax of palbociclib after repeated dose administration (Part C, D)
  • Cmax of palbociclib after repeated dose administration (Part C, D)
  • AUC0-24 of palbociclib after repeated dose administration (Part C, D)
  • Urine excretion of SAR439859 (Part B)
  • Cytochrome P450 3A (CYP3A) enzyme induction and inhibition (Part B)
  • CYP3A enzyme induction and inhibition (Part A, E)
  • ER occupancy at 18FES-PET imaging (Part A)
  • Non-progression rate at 6 months
  • Observation of tumor changes by FES PET and FDG PET scans
  • tmax of alpelisib after third dose (Part F, G)
  • Cmax of alpelisib after third dose (Part F, G)
  • AUC0-24 of alpelisib after third dose (Part F, G)
  • tmax of alpelisib after repeated dose administration (Part F, G)
  • Cmax of alpelisib after repeated dose administration (Part F, G)
  • AUC0-24 of alpelisib after repeated dose administration (Part F, G)

Enrollment

305

Study Start Date

September 20, 2017

Eligibility

  • Gender:     Female
  • Minimum age:     18 Years
  • Maximum age:     N/A
  • Healthy volunteers:     No

Sponsors

Sanofi

Source

Sanofi

Official title

A Phase 1/2 Study for the Safety, Efficacy, Pharmacokinetic and Pharmacodynamics Evaluation of SAR439859, Administered Orally as Monotherapy, Then in Combination With Other Anti-cancer Therapies in Postmenopausal Women With Estrogen Receptor-positive Advanced Breast Cancer (AMEERA-1)

Clinicaltrials.gov Identifier

NCT03284957

     

Source: Clinicaltrials.gov. Through our founding membership in the Dana-Farber/Harvard Cancer Center, an NCI-designated Comprehensive Cancer Center, these clinical trials are conducted at the Massachusetts General Hospital Cancer Center and may be available at other partner institutions.