Clinical trial NCT01636479: Phase 1 Safety Testing of SAR405838
Official title: A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Biological Activity of SAR405838 in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasm Malignant
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-07-10
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: SAR405838 Maximum tolerated dose (MTD)
timeFrame: Cycle 1 (21 days) or 2 Cycles (42 days) dependent on dosing schedule
measure: In MTD cohort, clinical benefit
timeFrame: Until disease progression
Secondary outcomes:
measure: Adverse events (eg, number of patients experiencing AEs)
timeFrame: Baseline to end of study
measure: PK parameters (Cmax, Tmax, AUC)
timeFrame: Baseline to end of study
measure: Biomarkers
timeFrame: Baseline to end of study
measure: Clinical response
timeFrame: Baseline to end of study
measure: Drug administration compliance
timeFrame: Baseline to end of study
Other outcomes:
Locations:
city: Boston
country: United States
facility: Investigational Site Number 840101
state: Massachusetts
city: Boston
country: United States
facility: Investigational Site Number 840001
state: Massachusetts
city: New York
country: United States
facility: Investigational Site Number 840002
state: New York
city: Villejuif
country: France
facility: Investigational Site Number 250001
city: Amsterdam
country: Netherlands
facility: Investigational Site Number 528001
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 528003
city: Utrecht
country: Netherlands
facility: Investigational Site Number 528002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.