Oral SAR245408 (XL147) and Oral MSC1936369B in Patients With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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Primary Objective: - To determine the maximum tolerated dose(s) (MTD) and the recommended Phase 2 dose(s) (RP2D) of SAR245408 and MSC1936369B when combined in adult subjects with locally advanced or metastatic solid tumors. Secondary Objective: To characterize the safety and tolerability of SAR245408 and MSC1936369B combination therapy administered orally to adult patients with locally advanced or metastatic solid tumors To evaluate the pharmacokinetic (PK) profile of SAR245408 and MSC1936369B when used in combination To evaluate the pharmacodynamic (PD) effect of the SAR245408/MSC1936369B combination by assessing target and pathway inhibition

Detailed Description
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The duration of the study will include a period for screening of up to a maximum of 28 days, a pretreatment evaluation period of up to 5 days, the on-treatment period, followed by a minimum of 30-day follow-up after the last study drug administration. The patient may continue study treatment until disease progression, unacceptable toxicity, or consent withdrawal. The study will have 2 parts: Part one - Dose Escalation Part Two - Expansion. At the defined maximum tolerated doses (MTD(s), additional patients will be enrolled to collect safety, Pharmacokinetic, and Pharmacodynamic data

Official Title
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A Phase 1 Dose Escalation Study of Combination Therapy With Oral SAR245408 (XL147) and Oral MSC1936369B in Patients With Locally Advanced or Metastatic Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: SAR245408 (XL147)
* Drug: MSC1936369B


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patient with advanced solid tumors for which there is no approved or curative therapy: has any advanced solid tumor with diagnosed alteration in 1 or more genes of the PI3K, and mitogen-activated protein kinase (MAPK) pathways and/or has a histologically or cytologically confirmed diagnosis of 1 of the following solid tumors: pancreatic, thyroid, colorectal, non-small cell lung, endometrial, renal, breast, ovarian carcinoma and melanoma Exclusion criteria: The patient has previously been treated with a PI3K inhibitor or a Mitogen-activated protein extracellular signal-regulated kinase (MEK) inhibitor The patient has received: Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anticancer therapy within 28 days or 5 half lives for noncytotoxics (whichever is shorter) of Day 1 of trial drug treatment (6 weeks for nitrosureas or mitomycin C) Any investigational agent within 28 days of Day 1 of trial drug treatment The patient is currently receiving anticoagulation therapy with therapeutic doses of warfarin (low-dose warfarin ≤1 mg/day, heparin, and low-molecular weight heparins are permitted) History of central nervous system metastases 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 retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), history of uveitis, or history of retinal vein occlusion, or has medically relevant abnormalities identified on screening ophthalmologic examination. 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Dose escalation phase The starting dose of SAR245408 will be 25-mg once daily (up to 200-mg). The starting dose of MSC1936369B will be 15- mg once daily (up to 90-mg) | Drug: SAR245408 (XL147)<br>* Pharmaceutical form:capsule and tablet Route of administration: oral<br>Drug: MSC1936369B<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 |
| --- | --- | --- |
| Identification of maximum tolerated dose |  | up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment emergent adverse events |  | up to 4 years | 
| Pharmakokinetic parameters of SAR245408: Cmax |  | up to 4 years | 
| Pharmakokinetic parameters of SAR245408: Tmax |  | up to 4 years | 
| Pharmakokinetic parameters of SAR245408:AUCι |  | up to 4 years | 
| Pharmakokinetic parameters of MSC1936369B: Cmax |  | up to 4 years | 
| Pharmakokinetic parameters of MSC1936369B: Tmax |  | up to 4 years | 
| Pharmakokinetic parameters of MSC1936369B: AUCι |  | up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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locally advanced or metastatic