The main purpose of the study is to evaluate the safety and tolerability (any toxicities and side effects) of SAR405838 and Pimasertib and that includes identifying the maximum safe and tolerable dose of the study drugs. Also to assess the anti-…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* SAR405838 / pimasertib MTD (Maximum Tolerated Dose) and RP2D (Recommended
Phase 2 Dose) as assessed by DLT (dose-limiting toxicity) and the biological
acitivities within the tested dose range.
* In RP2D cohort expansion, tumor response and duration, as defined by RECIST
1.1.
Secondary outcome
* Overall safety profile of SAR405838 / Pimasertib (adverse events)
* PK parameters (Cmax, Tmax, AUC)
* PD biomarkers (MIC-1, IL-8, pERK, PBMC)
* In dose escalation phase, tumor response and duration.
* Genetic status of TP53/Ras in tumor tissue and ctDNA at baseline and post
study drug treatment
Background summary
SAR405838 is a new anti-cancer study drug that may stop the growth of cancer by
causing cancer cell death or blocking cancer cell division. SAR405838 has only
shown its ability to slow or stop tumor growth or shrink tumor mass when tested
in animals models. Its efficacy in humans is currently unknown.
Pimasertib has only shown its ability to slow or stop timor growth or shrink
tumor mass when tested in animal models. Its efficacy in humans is currently
being confirmed.
This research study is the first combination use of SAR405838 and pimasertib in
the treatment of patients.
Study objective
The main purpose of the study is to evaluate the safety and tolerability (any
toxicities and side effects) of SAR405838 and Pimasertib and that includes
identifying the maximum safe and tolerable dose of the study drugs. Also to
assess the anti-tumor activities of SAR405838/ Pimasertib in patients with
advanced/ metastatic melanoma, non-small cell lung cancer (NSCLC), and
colorectal cancer (CRC) based on TP53 and Ras data in tumor tissue in cohort
expansion.
Other objectives of this study include evaluations of pharmacokinetics (PK) and
pharmacodynamics (PD). Also the anti-tumor acitvity in response to
SAR405838/Pimasertib will be investigated. In addition, TP53/Ras genetic
status in tumor tissue and tumor DNA (ctDNA) derived from plasma, both at
baseline and in response to SAR405838/ Pimasertib treatment.
Study design
This is a multicenter study being conducted in the Netherlands, France and
United States. It is an open-label study.
Approximately 94 patients will take part in the study in dose finding and
expansion phase.
The study consists of 3 parts:
* screening
* study treatment
* follow-up visit
The total duration of participation in the study will be approximately 14 to 30
weeks.
Intervention
SAR405838 will be taken at various doses orally once daily. Pimasertib will be
taken at various doses orally twice daily.
Study burden and risks
Risks are related to blood sampling and possible side effects of the study
drugs. The burden for the patient will be the number of visits to the research
site as part of the trial.
Kampenringweg 45E
Gouda 2803 PE
NL
Kampenringweg 45E
Gouda 2803 PE
NL
Listed location countries
Age
Inclusion criteria
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;
Exclusion criteria
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;
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-002325-33-NL |
| ClinicalTrials.gov | NCT01985191 |
| CCMO | NL45409.031.13 |