A Safety and Efficacy Study of SAR405838 and Pimasertib in Cancer Patients

A Phase 1 Study of Combination Therapy With SAR405838 and Pimasertib in Patients With Advanced Cancer

Primary Objectives:

To determine the recommended Phase 2 dose of SAR405838 / pimasertib combination therapy in patients with solid tumors.

To assess the anti-tumor activities of SAR405838 / pimasertib in patients with solid tumors.

Secondary Objectives:

To characterize the pharmacokinetic profile of SAR405838 and pimasertib.

To evaluate the pharmacodynamic effect of the SAR405838 and pimasertib.

To characterize genetic status in tumor tissue and circulating tumor DNA.

Study Overview

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

Detailed Description

The duration of the study for an individual patient will include a period to assess eligibility of up to 4 weeks, a treatment period of at least 6 weeks of study treatment, and an end-of-study visit at least 30 days (or until the patient receives another anti-cancer therapy, whichever is shorter) following the last administration of study drug.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Villejuif Cedex, 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

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.
• Presence of locally advanced or metastatic disease with at least one measurable lesion.
• Ability to provide written informed consent. Evidence of a personally signed informed consent.

Exclusion criteria:

• Age <18 years.
• Eastern Cooperative Oncology Group performance status of >1.
• Inadequate functions of bone marrow, liver, and kidney.
• Positive pregnancy test in women of child-bearing potential.
• Pregnancy or breast-feeding.
• Extensive prior radiotherapy.
• The patient has retinal degenerative disease, history of uveitis, or history of retinal vein occlusion, or history of retinal detachment, or has medically relevant abnormalities identified on screening ophthalmologic examination.
• Prior history of myositis or rhabdomyolysis.
• Recent major surgery or trauma, unhealing/open wounds.
• The patient has had congestive heart failure, unstable angina, a myocardial infarction, cardiac conduction abnormality or pacemaker or a stroke within 3 months of entering the study.
• The patient has a baseline corrected QT interval (QTc) >480 ms or left ventricular ejection fraction (LVEF) <50% or less than the lower limit of normal.
• The patient has a previously-identified allergy or hypersensitivity to components of the study treatment formulations.
• Unwillingness or inability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
• 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 history of acute pancreatitis.
• Clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that could affect the safety of the patient; alter the absorption of the study drugs; or impair the assessment of study results.

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: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; SAR405838 and pimasertib in escalating doses	Drug: SAR405838; Pharmaceutical form:capsule Route of administration: oral; Drug: Pimasertib; Pharmaceutical form: capsule Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
SAR405838 (pimasertib) RP2D assessed by dose-limiting toxicities and pharmacological activities	6 weeks for each patient at each dose level
Changes of tumor dimension by imaging	At least 3 months for each patient

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall safety profile of SAR405838 (pimasertib), number of participants with adverse events	Throughout the study
Pharmacokinetic parameters for both SAR405838 (pimasertib): the maximum concentration in blood (Cmax)	3 months for each patient
Pharmacokinetic parameters for both SAR405838 (pimasertib): time to the maximum concentration (Tmax)	3 months for each patient
Pharmacokinetic parameters for both SAR405838 (pimasertib): area under the curve (AUC), etc.	3 months for each patient
Biomarker changes in response to SAR405838 (pimasertib) treatment	3 months for each patient
Genetic status in tumor tissue	Baseline
Change of the genetic status of circulating tumor DNA	Baseline and until disease progression

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Merck KGaA, Darmstadt, Germany

Publications and helpful links

General Publications

• de Weger VA, de Jonge M, Langenberg MHG, Schellens JHM, Lolkema M, Varga A, Demers B, Thomas K, Hsu K, Tuffal G, Goodstal S, Mace S, Deutsch E. A phase I study of the HDM2 antagonist SAR405838 combined with the MEK inhibitor pimasertib in patients with advanced solid tumours. Br J Cancer. 2019 Feb;120(3):286-293. doi: 10.1038/s41416-018-0355-8. Epub 2018 Dec 26.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: October 31, 2013
• First Submitted That Met QC Criteria: November 8, 2013
• First Posted (Estimate): November 15, 2013

Study Record Updates

• Last Update Posted (Estimate): February 25, 2016
• Last Update Submitted That Met QC Criteria: February 24, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TCD13388; 2013-002325-33; U1111-1144-8349 (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