A Safety and Efficacy Study of SAR405838 and Pimasertib in Cancer Patients
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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 Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
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:
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Age <18 years.
-
Eastern Cooperative Oncology Group performance status of >1.
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Inadequate functions of bone marrow, liver, and kidney.
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Positive pregnancy test in women of child-bearing potential.
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Pregnancy or breast-feeding.
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Extensive prior radiotherapy.
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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.
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Prior history of myositis or rhabdomyolysis.
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Recent major surgery or trauma, unhealing/open wounds.
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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.
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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.
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The patient has a previously-identified allergy or hypersensitivity to components of the study treatment formulations.
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Unwillingness or inability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
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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.
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Recent history of acute pancreatitis.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site Number 250001 | Villejuif Cedex | France | 94805 | |
| 2 | Investigational Site Number 528001 | Amsterdam | Netherlands | 1066 CX | |
| 3 | Investigational Site Number 528003 | Rotterdam | Netherlands | 3075 EA | |
| 4 | Investigational Site Number 528002 | Utrecht | Netherlands | 3584 CX |
Sponsors and Collaborators
- Sanofi
- Merck KGaA, Darmstadt, Germany
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TCD13388
- 2013-002325-33
- U1111-1144-8349