Phase 1 Safety Testing of SAR405838

Study Overview
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Brief Summary
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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.

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

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

Conditions
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Neoplasm Malignant

Intervention / Treatment
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* Drug: SAR405838


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAR405838<br>SAR405838 in escalating doses | Drug: SAR405838<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |