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

Neoplasm Malignant Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01985191
• Other study ID #: TCD13388
• Secondary ID: 2013-002325-33U1
• Status: Completed
• Phase: Phase 1
• First received: October 31, 2013
• Last updated: February 24, 2016
• Start date: November 2013
• Est. completion date: February 2016

Study information

• Verified date: February 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Committee for the Protection of Personnes
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasm Malignant
• Neoplasms

Intervention

Drug:
• SAR405838
Pharmaceutical form:capsule Route of administration: oral
• Pimasertib
Pharmaceutical form: capsule Route of administration: oral

Locations

Country	Name	City	State
France	Investigational Site Number 250001	Villejuif Cedex
Netherlands	Investigational Site Number 528001	Amsterdam
Netherlands	Investigational Site Number 528003	Rotterdam
Netherlands	Investigational Site Number 528002	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Merck KGaA

Countries where clinical trial is conducted

France,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SAR405838 (pimasertib) RP2D assessed by dose-limiting toxicities and pharmacological activities		6 weeks for each patient at each dose level	No
Primary	Changes of tumor dimension by imaging		At least 3 months for each patient	No
Secondary	Overall safety profile of SAR405838 (pimasertib), number of participants with adverse events		Throughout the study	Yes
Secondary	Pharmacokinetic parameters for both SAR405838 (pimasertib): the maximum concentration in blood (Cmax)		3 months for each patient	No
Secondary	Pharmacokinetic parameters for both SAR405838 (pimasertib): time to the maximum concentration (Tmax)		3 months for each patient	No
Secondary	Pharmacokinetic parameters for both SAR405838 (pimasertib): area under the curve (AUC), etc.		3 months for each patient	No
Secondary	Biomarker changes in response to SAR405838 (pimasertib) treatment		3 months for each patient	No
Secondary	Genetic status in tumor tissue		Baseline	No
Secondary	Change of the genetic status of circulating tumor DNA		Baseline and until disease progression	No