E7080 in Combination With Carboplatin and Paclitaxel in Patients With Non-small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The purpose of this study is to determined the maximum tolerated dose (MTD), safety and tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor effect of E7080 administered continually twice daily in combination with carboplatin and paclitaxel to patients with advanced or metastatic non-small cell lung cancer.

Official Title
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E7080 in Combination With Carboplatin and Paclitaxel in Patients With Non-small Cell Lung Cancer (NSCLC)

Conditions
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Non-small-cell Lung Cancer

Intervention / Treatment
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* Drug: E7080
* Drug: E7080
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subjects with a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC). Locally advanced and/or metastatic non-small cell lung cancer (NSCLC) (Stage IIIB/IV). Subjects with at least one measurable tumor lesion by Response Evaluation Criteria In Solid Tumors (RECIST). Subjects with Performance Status (PS) 0-1. Subjects with adequate organ function. Exclusion criteria: Subjects who have ever received the following therapy for non-small cell lung cancer (NSCLC): Chemotherapy Biological or immunotherapies Surgery for primary focus The radiation therapy for primary focus Subjects with the severe complications or disease history. Subjects with brain metastasis accompanying clinical symptoms or requiring treatment. Subjects with simultaneous or metachronous cancers. Subjects who cannot take oral medication. Subjects who are using drugs that strongly inhibit or induce cytochrome P450 (CYP) 3A4.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E7080 (Dose Escalation Cohort)<br>This will be a dose-escalation evaluation of 12-18 participants to determine the maximum tolerated dose of E7080 in combination with paclitaxel and carboplatin. | Drug: E7080<br>* Drug: E7080 will be administered orally starting at a dose of 6 mg twice daily during the 7-day run-in period and for 3 weeks (Cycle 1).<br>Drug: Paclitaxel<br>* Paclitaxel (200 mg/m2) will be administered intravenously (IV) on Day 1 after administration of E7080.<br>Drug: Carboplatin<br>* Carboplatin (AUC 6.0 min/mg/mL) will be administered IV on Day 1 after administration of E7080 and Paclitaxel.<br>|
| Experimental: E7080 (Expansion Cohort)<br>Dosage of E7080 for Expansion Cohort will be determined based on the maximum tolerated dose in the Dose-Escalation Cohort. | Drug: E7080<br>* Maximum tolerated dose determined in the Dose-Escalation Cohort will be administered to the Expansion Cohort. After E7080 is taken on Day 1, paclitaxel (200 mg/m2) will be administered intravenously (IV), followed by IV carboplatin (AUC 6.0 min/mg/mL).<br>Drug: Paclitaxel<br>* Paclitaxel (200 mg/m2) will be administered intravenously (IV) on Day 1 after administration of E7080.<br>Drug: Carboplatin<br>* Carboplatin (AUC 6.0 min/mg/mL) will be administered IV on Day 1 after administration of E7080 and Paclitaxel.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | Tolerability was confirmed by the frequency of occurrence of Dose Limiting Toxicities (DLTs) observed by the end of Cycle 1 in 6 participants. | 7 days during the run-in period (Cycle 0) and 3 weeks (21 days) from Cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumor Effect of E7080 in Combination With Carboplatin and Paclitaxel. |  | At Screening, on Day 22 of every even cycle, and at discontinuation | 
| Pharmacokinetics and Pharmacodynamics of E7080 in Combination With Carboplatin and Paclitaxel. |  | At various time points until Day 22 of Cycle 1 | 
| To Evaluate the Safety and Tolerability of E7080 in Combination With Carboplatin and Paclitaxel. | Refer safety section for safety analysis | Throughout the study until 30 days after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Lung Cancer