Phase 1 Safety Testing of SAR405838

A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Biological Activity of SAR405838 in Patients With Advanced Cancer

Primary Objectives:

• To determine safety and the maximum tolerated dose (MTD) of SAR405838 through the characterization of dose-limiting toxicities (DLTs).
• To assess biological activities in patients with dedifferentiated liposarcoma during MTD cohort expansion.

Secondary Objectives:

• Pharmacokinetic (PK) profile of SAR405838.
• Biomarkers in association with SAR405838.
• Anti-tumor activity in response to SAR405838.
• Food effect on SAR405838 PK.
• Compliance with SAR405838 treatment.
• Cytochrome P450 3A4/5 (CYP3A4/5) activity.

Study Overview

• Status: Completed
• Conditions: Neoplasm Malignant
• Intervention / Treatment: Drug: SAR405838

Detailed Description

Total duration of study participation for each patient will be one month screening followed by treatment until precluded by toxicity, noncompliance, progression, or death.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Villejuif, France, 94805
    • Investigational Site Number 250001
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Investigational Site Number 528001
  • Rotterdam, Netherlands, 3075 EA
    • Investigational Site Number 528003
  • Utrecht, Netherlands, 3584 CX
    • Investigational Site Number 528002
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Investigational Site Number 840101
    • Boston, Massachusetts, United States, 02115
      • Investigational Site Number 840001
  • New York
    • New York, New York, United States, 10021
      • Investigational Site Number 840002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Histologically or cytologically confirmed diagnosis of a solid tumor for which no further effective standard treatment is available. Patients with lymphomas may be enrolled.
• For dose escalation, tumor type that has high biomarker prevalence without molecular confirmation of biomarker status, or any tumor type with molecular confirmation of biomarker status; For MTD cohort expansion, only dedifferentiated liposarcoma will be included.
• Presence of locally advanced or metastatic disease with at least one measurable lesion.

Exclusion criteria:

• Age <18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of >1.
• Life expectancy <12 weeks.
• Unstable brain or leptomeningeal disease based on history and physical examination.
• Inadequate organ functions, positive pregnancy test.
• Pregnancy or breast-feeding.
• Any anti-cancer drug therapy within 2 weeks (8 weeks for mitomycin C or nitrosoureas) or 5 half-lives of the drug prior to study treatment, whichever is shorter, prior to study treatment.
• Unwillingness, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ an effective barrier or medical method of contraception during the study drug administration and follow-up periods.
• Recent (3 months) history of acute pancreatitis.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR405838; SAR405838 in escalating doses	Drug: SAR405838; Pharmaceutical form: Capsule Route of administration: Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
SAR405838 Maximum tolerated dose (MTD)	Cycle 1 (21 days) or 2 Cycles (42 days) dependent on dosing schedule
In MTD cohort, clinical benefit	Until disease progression

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events (eg, number of patients experiencing AEs)	Baseline to end of study
PK parameters (Cmax, Tmax, AUC)	Baseline to end of study
Biomarkers	Baseline to end of study
Clinical response	Baseline to end of study
Drug administration compliance	Baseline to end of study

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• de Jonge M, de Weger VA, Dickson MA, Langenberg M, Le Cesne A, Wagner AJ, Hsu K, Zheng W, Mace S, Tuffal G, Thomas K, Schellens JH. A phase I study of SAR405838, a novel human double minute 2 (HDM2) antagonist, in patients with solid tumours. Eur J Cancer. 2017 May;76:144-151. doi: 10.1016/j.ejca.2017.02.005. Epub 2017 Mar 17.

Study record dates

Study Major Dates

• Study Start: July 13, 2012
• Primary Completion (Actual): March 5, 2018
• Study Completion (Actual): March 5, 2018

Study Registration Dates

• First Submitted: July 2, 2012
• First Submitted That Met QC Criteria: July 5, 2012
• First Posted (Estimate): July 10, 2012

Study Record Updates

• Last Update Posted (Actual): May 17, 2018
• Last Update Submitted That Met QC Criteria: May 16, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TED12318; 2012-000733-39; U1111-1127-2911 (Other Identifier: UTN)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No