A Phase 1 Study of Combination Therapy with SAR405838 and Pimasertib in Patients with Advanced Cancer
- Conditions
- advanced cancer10027656
- Registration Number
- NL-OMON40404
- Lead Sponsor
- Sanofi-aventis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 42
Histologically or cytologically confirmed diagnosis of a solid tumor;
Presence of locally advanced or metastatic disease with at least one measurable lesion that is not responsive to standard therapies or for which no approved or curative therapy is available.
Ability to provide written informed consent. Evidence of a personally signed informed consent;
Age < 18 years;
Eastern Cooperative Oncology Group performance status > 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;
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>* SAR405838 / pimasertib MTD (Maximum Tolerated Dose) and RP2D (Recommended<br /><br>Phase 2 Dose) as assessed by DLT (dose-limiting toxicity) and the biological<br /><br>acitivities within the tested dose range.<br /><br>* In RP2D cohort expansion, tumor response and duration, as defined by RECIST<br /><br>1.1.</p><br>
- Secondary Outcome Measures
Name Time Method <p>* Overall safety profile of SAR405838 / Pimasertib (adverse events)<br /><br>* PK parameters (Cmax, Tmax, AUC)<br /><br>* PD biomarkers (MIC-1, IL-8, pERK, PBMC)<br /><br>* In dose escalation phase, tumor response and duration.<br /><br>* Genetic status of TP53/Ras in tumor tissue and ctDNA at baseline and post<br /><br>study drug treatment</p><br>