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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Neoplasm Malignant

Intervention / Treatment
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* Drug: SAR405838
* Drug: Pimasertib


Participation Criteria
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Eligibility Criteria
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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.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>SAR405838 and pimasertib in escalating doses | Drug: SAR405838<br>* Pharmaceutical form:capsule Route of administration: oral<br>Drug: Pimasertib<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 (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 | Measure Description | 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 |