CS-7017 in Combination With Carboplatin/Paclitaxel in Subjects With Stage IIIb/IV Non-small Cell Lung Cancer (NSCLC)

Phase 1

Completed

Conditions: Carcinoma, Non-Small-Cell Lung

Interventions: Drug: CS-7017
Drug: Carboplatin
Drug: Paclitaxel

Registration Number: NCT01199055

Lead Sponsor: Daiichi Sankyo Co., Ltd.

Brief Summary: The primary objectives of this study are to evaluate the safety and tolerability of CS-7017 administered orally twice a day in combination with carboplatin and paclitaxel, and to assess the pharmacokinetics of CS-7017 in combination with carboplatin and paclitaxel.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

Inclusion Criteria

Histologically or cytologically confirmed unresectable locally advanced or metastatic (stage IIIb or IV) non-small cell lung cancer (NSCLC)
No prior systemic therapy for NSCLC
Male or female ≥ 18 years of age
Anticipation of more than 3 months survival
Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1
Adequate organ and bone marrow function

Exclusion Criteria

Anticipation of need for a major surgical procedure or radiation therapy during the study
Remaining influence of previous therapies such as radiotherapy, surgery, immunotherapy within 4 weeks prior to start of study treatment
History of any of the following events within 6 months prior to start of study treatment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class ≥I congestive heart failure (CHF), cerebrovascular accident or cerebral infarction, pulmonary embolism, deep vein thrombosis, or other clinically significant thromboembolic event; clinically significant pulmonary disease (eg, severe chronic-obstructive pulmonary disease (COPD) or asthma)
Severe edema, ascites fluid, pericardial or pleural effusion or pericardial involvement with the tumor within 6 months prior to start of study treatment, or which require steroid therapy/ diuretic therapy
Subjects with brain metastasis (defined as untreated, symptomatic or requiring steroids or anticonvulsant medications to control associated symptoms)
Subjects with clinically significant active infection which requires antibiotic therapy, or who are hepatitis B surface antigen (HBs)- or hepatitis C virus (HCV)- or human immunodeficiency virus (HIV)- positive and receiving antiretroviral therapy
Subjects with malabsorption syndrome, chronic diarrhea (lasting over 4 weeks), inflammatory bowel disease, or partial bowel obstruction
Diabetes mellitus requiring insulin, or a history of poor serum glucose control with the use of non-insulin diabetes medications
Treatment with thiazolidinediones (TZDs) within 4 weeks prior to start of study treatment
History of a second malignancy, with the exception of in situ cervical cancer or adequately treated basal cell or squamous cell carcinoma of the skin
Poorly-controlled blood pressure as judged by the Investigator

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CS-7017+Carboplatin/Paclitaxel	Paclitaxel	Drug: CS-7017 from 0.25 mg twice a day (BID) to 0.50 mg BID for up to 4\~6 cycles (1 cycle: 3 weeks) Drug: Carboplatin IV, Area under the curve (AUC) of 6 mg/mL\*min, once every three weeks for up to 4\~6 cycles (1 cycle: 3 weeks) Drug: Paclitaxel IV, 200mg/m\^2, once every three weeks for up to 4\~6 cycles (1 cycle: 3 weeks)
CS-7017+Carboplatin/Paclitaxel	CS-7017	Drug: CS-7017 from 0.25 mg twice a day (BID) to 0.50 mg BID for up to 4\~6 cycles (1 cycle: 3 weeks) Drug: Carboplatin IV, Area under the curve (AUC) of 6 mg/mL\*min, once every three weeks for up to 4\~6 cycles (1 cycle: 3 weeks) Drug: Paclitaxel IV, 200mg/m\^2, once every three weeks for up to 4\~6 cycles (1 cycle: 3 weeks)
CS-7017+Carboplatin/Paclitaxel	Carboplatin	Drug: CS-7017 from 0.25 mg twice a day (BID) to 0.50 mg BID for up to 4\~6 cycles (1 cycle: 3 weeks) Drug: Carboplatin IV, Area under the curve (AUC) of 6 mg/mL\*min, once every three weeks for up to 4\~6 cycles (1 cycle: 3 weeks) Drug: Paclitaxel IV, 200mg/m\^2, once every three weeks for up to 4\~6 cycles (1 cycle: 3 weeks)

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic Parameter Observed Serum Concentration (Cmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer	Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose	The maximum serum concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D).
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Geometric Means of Serum Free Form of CS-7017 (R-150033) After Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer	Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose	The area under the concentration versus time curve during dosing interval (AUCtau) and up to the last quantifiable time (AUClast) of geometric means of CS-7017 are reported at selected cycles (C) and days (D).
Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer	Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose	The time of maximum plasma concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D).
Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group During Cycle 1 Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer	Baseline to end of Cycle 1, with each treatment cycle being 3 weeks	Treatment-emergent adverse events (TEAEs) are defined as those adverse events that occur, having been absent before the study, or worsen in severity after the initiation of study drug.

Secondary Outcome Measures

Name	Time	Method
Best Overall Response and Objective Response Rate Following Administration of CS-7017 in Combination With Carboplatin/Paclitaxel in Chemotherapy-naïve Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC)	Baseline up to Week 18 postdose	The best overall response is the best response (in the order of confirmed complete response \[CR\], confirmed partial response \[PR\], stable disease \[SD\], and progressive disease \[PD\]) among all overall responses from the start of treatment until the participant withdraws from the study. Participants who did not have a tumor assessment, the best overall response is Not Evaluable (NE). The response rate was defined as the proportion of participants with a best overall response of CR or PR, ie, \[confirmed and unconfirmed, (CR + PR) / number of participants\]. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, CR was defined as the disappearance of all target lesions, PR was defined as ≥30% decrease in the sum of diameters of target lesions, PD was defined as ≥20 increase in the smallest sum of diameters, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
CS-7017-Related Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group After Administration of CS-7017 and Carboplatin/Paclitaxel in Chemotherapy-naïve Participants With Stage IIIb/IV Non-small Cell Lung Cancer	Baseline to 30 days after last dose, up to approximately 1 year	Treatment-emergent adverse events (TEAEs) are defined as those adverse events that occur, having been absent before the study, or worsen in severity after the initiation of study drug. CS-7017-related TEAEs are those TEAEs that are related to CS-7017 in the relationship.