Study of Carboplatin/Paclitaxel With or Without Investigational Drug (CS-7017) in Subjects With Metastatic Non-small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The study has a safety and a Phase 2 portion. In the safety portion of the study, subjects with metastatic non-small cell lung cancer will be treated with study drug (CS-7017) in combination with carboplatin and paclitaxel to evaluate safety. In the Phase 2 portion of the study, subjects will receive study drug (CS-7017) or placebo in combination with carboplatin and paclitaxel to evaluate effectiveness and safety. The study will find out if adding CS-7017 to carboplatin and paclitaxel will be safe and improve progression free survival in subjects with metastatic non-small cell lung cancer.

Official Title
-----------------
Phase 2 Randomized Study of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-Naïve Subjects With Metastatic Non-Small Cell Lung Cancer

Conditions
-----------------
Metastatic Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: CS7017 tablets
* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: Placebo Tablets


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed metastatic (stage IV) NSCLC with no significant pleural effusion or pleural involvement from the tumor Age greater than or equal to 18 years Adequate organ and bone marrow function Exclusion Criteria: Any prior systemic therapy for NSCLC Major surgical procedure or other investigational agents within 4 weeks before study enrollment Need for concomitant use of other thiazolidinediones during the study History of any of the following conditions within 6 months prior to initiating study treatment: Diabetes mellitus requiring treatment with insulin or sulfonylureas or thiazolidinediones (TZDs) agents; Myocardia infarction with significant impairment of cardia function; Malabsorption syndrome, chronic diarrhea, inflammatory bowel disease or partial bowel obstruction; Clinically active brain metastases, uncontrolled seizure disorder; spinal cord compression or carcinomatous meningitis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CS-7017 with Paclitaxel and Carboplatin<br> | Drug: CS7017 tablets<br>* CS7017 tablets, strength 0.25 mg, two tablets, two times daily for twenty-five to thirty months<br>Drug: Paclitaxel<br>* Intravenous (IV), 200 mg/m^2, once every three weeks for up to 18 weeks<br>Drug: Carboplatin<br>* IV, area under the curve (AUC) of 6, once every three weeks for up to 18 weeks<br>|
| Placebo Comparator: Paclitaxel and Carboplatin<br> | Drug: Paclitaxel<br>* Intravenous (IV), 200 mg/m^2, once every three weeks for up to 18 weeks<br>Drug: Carboplatin<br>* IV, area under the curve (AUC) of 6, once every three weeks for up to 18 weeks<br>Drug: Placebo Tablets<br>* Placebo tablets matching CS-7017 tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Progression-Free Survival at 18 Weeks Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer | Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of the first objective documentation of disease progression (based upon radiographic tumor assessments) or death. As per Response Evaluation Criteria for Solid Tumors v1.0, disease progression was characterized as confirmed complete response (CR) defined as disappearance of all target lesions, confirmed partial response (PR) defined as ≥30% decrease from baseline, stable disease (SD) defined as neither progressive disease (PD) nor PR, and PD defined as ≥20% increase from smallest sum of longest diameter recorded since treatment started. | 18 weeks postdose | 
| Percentage of Participants With Progression-Free Survival Based on Radiologic and Clinical Assessments and Death After Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer | Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of the first objective documentation of disease progression (based upon radiographic tumor assessments) or death. Disease progression was determined in accordance with the RECIST version 1.0 criteria. | 18 weeks postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Kaplan-Meier Analysis of Overall Survival Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer | Overall survival (OS) is defined as the time from randomization to the date of death resulting from any cause. | Baseline to date of death, up to approximately 2 years postdose | 
| Number of Participants With Best Overall Tumor Response and Objective Response Rate Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer | As per Response Evaluation Criteria for Solid Tumors v1.0, the best overall response was characterized as confirmed complete response (CR) defined as disappearance of all target lesions, confirmed partial response (PR) defined as ≥30% decrease from baseline, stable disease (SD) defined as neither progressive disease (PD) nor PR, and PD defined as ≥20% increase from smallest sum of longest diameter recorded since treatment started. Objective response rate (ORR) was defined as CR + PR. | Baseline to disease progression, death, or withdrawal from study, up to approximately 2 years postdose | 
| Number of Participants With Treatment-Emergent Adverse Events Related to CS-7017/Placebo Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer |  | Baseline up to approximately 2 years postdose |