A Study of the Safety and Pharmacokinetics of SAR245409 Tablets in Patients With Solid Tumors or Lymphoma

Study Overview
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Brief Summary
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Primary Objective: - To evaluate the safety and tolerability of SAR245409 tablets administered once or twice a day in patients with solid tumors or lymphoma. Secondary Objectives: To evaluate blood levels of SAR245409 after administration of SAR245409 tablets once or twice a day in patients with solid tumors or lymphoma. To evaluate the effect of food on blood levels of SAR245409 after administration of SAR245409 tablets in patients with solid tumors or lymphoma. To evaluate the effect of SAR245409 on the body after administration of SAR245409 tablets once or twice a day in patients with solid tumors or lymphoma. To obtain information on how SAR245409 administered once or twice a day to patients with solid tumors or lymphoma affect disease symptoms and study treatment side effects as reported by the patients on a questionnaire. To explore the antitumor activity of SAR245409 tablets administered once or twice a day to patients with solid tumors or lymphoma.

Detailed Description
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The total study duration per patient will be 58 to 128 days and will include a screening period (1 to 28 days), a food interaction investigation period (when applicable; 4 to 11 days), two 28-day treatment cycles (56 days), an end-of-treatment visit (within 7 days after the last SAR245409 administration) and a follow-up visit (within 30 ± 3 days after the last SAR245409 administration).

Official Title
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A Phase 1 Dose-escalation Study of the Safety and Pharmacokinetics of a Tablet Formulation of SAR245409 Administered Daily to Patients With Solid Tumors or Lymphoma

Conditions
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Neoplasm Malignant

Intervention / Treatment
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* Drug: SAR245409


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Solid tumor that is metastatic or unresectable, or relapsed or refractory lymphoma (including chronic lymphocytic leukemia/small lymphocytic lymphoma), for which standard therapies are no longer effective or there are no therapies known to prolong survival. Male or female patient > or = 18 years old. Eastern Cooperative Oncology Group Performance Status < or = 1. Adequate white blood cells, platelets and haemoglobin. Adequate liver and kidney functions. Fasting plasma glucose < 160 mg/dL. No other malignancy. Women of childbearing potential using adequate contraception. Exclusion criteria: History of partial or full gastrectomy. Lymphoma involving the gastrointestinal tract. Uncontrolled brain metastases or a primary brain tumor. Prior treatment with cytotoxic chemotherapy (including investigational agents) or biologic agents (antibodies, immune modulators, and cytokines) within 4 weeks, or nitrosoureas or mitomycin C within 6 weeks, before the first dose of study treatment. Prior treatment with a small-molecule kinase inhibitor (including investigational agents) within 2 weeks, or 5 half lives of the drug or active metabolites, whichever is longer, before the first dose of study treatment. Any other investigational therapy within 4 weeks before the first dose of study treatment. Prior anticancer hormonal therapy within 1 week before the first dose of study treatment. Prior radiation therapy within 2 weeks before the first dose of study treatment. Intolerance of prior treatment with a PI3K inhibitor. Hereditary or acquired immunodeficiency syndrome or HIV (human immunodeficiency virus) infection. Lymphoma patients with positive serologies for Hepatitis B surface antigen (HBsAg) or anti-Hepatitis C virus (anti-HCV) antibodies. Positive serologies for Hepatitis B surface antigen (HBsAg) or anti-Hepatitis C virus (anti-HCV) antibodies. Patient is pregnant or breastfeeding. 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

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Once daily dosing<br>escalating doses, once daily dosing every day, no eating for 2 hours prior and 1 hour after dose | Drug: SAR245409<br>* Pharmaceutical form: tablet Route of administration: oral<br>|
| Experimental: Twice daily dosing<br>escalating doses, twice daily dosing every day, no eating for 2 hours prior and 1 hour after dose | Drug: SAR245409<br>* Pharmaceutical form: tablet Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities |  | Up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with treatment-emergent adverse events |  | From first dose of SAR245409 until 30 days after the last dose | 
| Maximum SAR245409 plasma concentration |  | Cycle 1 Days 1, 2, 8, 15, and 28, and Cycle 2 Day 1 | 
| Area under the SAR245409 plasma concentration versus time curve |  | Cycle 1 Days 1, 2, 8, 15, and 28, and Cycle 2 Day 1 | 
| Ratio of maximum SAR245409 plasma concentration between fed and fasted dosing |  | Days 1, 2, 3, and 4 of the food interaction period | 
| Ratio of area under the SAR245409 plasma concentration versus time curve between fed and fasted dosing |  | Days 1, 2, 3, and 4 of the food interaction period |