Safety Study of XL147 (SAR245408), in Combination With Paclitaxel and Carboplatin in Adults With Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of XL147 in combination with paclitaxel and carboplatin in adults with solid tumors. XL147 is a new chemical entity that inhibits PI3 Kinase. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells. In clinical practice, the combination of paclitaxel and carboplatin is an accepted treatment regimen for various solid tumors, including ovarian cancer, endometrial cancer and non-small cell lung cancer (NSCLC).

Official Title
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A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL147 (SAR245408) in Combination With Paclitaxel and Carboplatin in Subjects With Solid Tumors

Conditions
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Cancer, Non-Small Cell Lung Cancer, Endometrial Carcinoma, Ovarian Carcinoma

Intervention / Treatment
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* Drug: XL147 (SAR245408),
* Drug: paclitaxel
* Drug: carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of: Advanced solid tumor that is no longer responding to therapies OR Advanced or recurrent endometrial carcinoma OR Advanced or recurrent ovarian carcinoma OR Unresectable (Stage IIIB or IV) NSCLC ECOG Performance Status 0-1 (ECOG status of 2 may be considered following discussion and agreement with sponsor) Adequate organ and bone marrow function as defined by hematological and serum chemistry limits At least 18 years old Both men and women must practice adequate contraception Informed consent Exclusion Criteria: Restriction of some therapies/medications within specific timeframes prior to enrollment and during the study including prior therapy with PI3K, AKT, or mTOR inhibitors, cytotoxic chemotherapy, biologic agents, nitrosoureas or mitomycin C, small-molecule kinase inhibitors, non-cytotoxic hormonal agents Known allergy or hypersensitivity to any of the components of the treatment formulations Taking oral corticosteroids chronically or > 1 mg/day warfarin Not recovered from the toxic effects of prior therapy History of diabetes mellitus. Uncontrolled intercurrent illness Pregnant or breastfeeding Congestive heart failure, unstable angina, or a myocardial infarction within 3 months of entering the study. HIV positive Diagnosis of another malignancy may exclude subject from study

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: XL147 (SAR245408),<br>* Gelatin capsules supplied in 25- and 100-mg strengths; daily dosing<br>Drug: paclitaxel<br>* Intravenous injection dosed once every three weeks<br>* Other names: Taxol®;Drug: carboplatin<br>* Intravenous injection dosed once every three weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety, tolerability, and MTD of XL147 administered in combination with paclitaxel (at doses up to 175 mg/m2) and carboplatin in subjects with advanced solid tumors |  | Assessed at periodic visits | 
| To evaluate the safety, tolerability, and MTD of XL147 administered in combination with paclitaxel (at doses up to 225 mg/m2) and carboplatin in subjects with NSCLC |  | Assessed at periodic visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the relationship between selected biomarkers and efficacy and safety outcomes |  | Assessed at periodic visits | 
| To assess plasma pharmacokinetics (PK) of XL147, paclitaxel, and carboplatin when used in combination |  | Assessed at periodic visits | 
| To evaluate preliminary antitumor activity of XL147 in combination with carboplatin and paclitaxel |  | Assessed at periodic visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumors, NSCLC, Ovarian Cancer, Endometrial Cancer