Non-small-cell Lung Cancer
Conditions
Keywords
Cancer, Lung Cancer
Brief summary
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.
Interventions
DRUGE7080
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).
DRUGPaclitaxel
Paclitaxel (200 mg/m2) will be administered intravenously (IV) on Day 1 after administration of E7080.
DRUGCarboplatin
Carboplatin (AUC 6.0 min/mg/mL) will be administered IV on Day 1 after administration of E7080 and Paclitaxel.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects with a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC). 2. Locally advanced and/or metastatic non-small cell lung cancer (NSCLC) (Stage IIIB/IV). 3. Subjects with at least one measurable tumor lesion by Response Evaluation Criteria In Solid Tumors (RECIST). 4. Subjects with Performance Status (PS) 0-1. 5. Subjects with adequate organ function.
Exclusion criteria
1. Subjects who have ever received the following therapy for non-small cell lung cancer (NSCLC): 1. Chemotherapy 2. Biological or immunotherapies 3. Surgery for primary focus 4. The radiation therapy for primary focus 2. Subjects with the severe complications or disease history. 3. Subjects with brain metastasis accompanying clinical symptoms or requiring treatment. 4. Subjects with simultaneous or metachronous cancers. 5. Subjects who cannot take oral medication. 6. Subjects who are using drugs that strongly inhibit or induce cytochrome P450 (CYP) 3A4.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 7 days during the run-in period (Cycle 0) and 3 weeks (21 days) from Cycle 1 | Tolerability was confirmed by the frequency of occurrence of Dose Limiting Toxicities (DLTs) observed by the end of Cycle 1 in 6 participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Throughout the study until 30 days after last dose | Refer safety section for safety analysis |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| E7080 4 mg BID (Dose Escalation) E7080 mono-therapy (initial dose was 4 mg BID) was orally administered twice daily for 7 days in run-in period (Cycle 0); subsequently from Cycle 1 but up to 6 Cycles, E7080 treatment was continued with the combination of carboplatin (Area under the curve (AUC) 6.0 min/mg/mL) and paclitaxel (200 mg/m2) on Day 1 every 3 weeks. | 6 |
| E7080 6 mg BID (Dose Escalation) E7080 mono-therapy (initial dose was 6 mg BID) was orally administered twice daily for 7 days in run-in period (Cycle 0); subsequently from Cycle 1 but up to 6 Cycles, E7080 treatment was continued with the combination of carboplatin (AUC 6.0 min/mg/mL) and paclitaxel (200 mg/m2) on Day 1 every 3 weeks. | 6 |
| E7080 4 mg BID (Expansion) Dosage of E7080 for expansion cohort was determined based on the maximum tolerated dose (MTD). The MTD for E7080 with with the combination of carboplatin and paclitaxel was 4 mg BID (Arm 1). For the expansion cohort, run-in treatment (Cycle 0) was not performed and E7080 treatment (4 mg BID) began from Cycle 1 but up to 6 Cycles with the combination of carboplatin (AUC 6.0 min/mg/mL) and paclitaxel (200 mg/m2) on Day 1 every 3 weeks. | 16 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | E7080 4 mg BID (Dose Escalation) | E7080 6 mg BID (Dose Escalation) | E7080 4 mg BID (Expansion) | Total |
|---|---|---|---|---|
| Age, Continuous | 52.8 Years STANDARD_DEVIATION 9.3 | 54.8 Years STANDARD_DEVIATION 9.7 | 58.4 Years STANDARD_DEVIATION 11.2 | 56.4 Years STANDARD_DEVIATION 10.4 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 13 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 16 / 16 |
| serious Total, serious adverse events | 3 / 6 | 2 / 6 | 6 / 16 |
Outcome results
Primary
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.
Time frame: 7 days during the run-in period (Cycle 0) and 3 weeks (21 days) from Cycle 1
Population: DLTs were analyzed on the Safety Analysis Set; however subjects with 75% or less treatment compliance for E7080 in Cycle 1 or those who discontinued the study and had no confirmed data on tolerability up to Cycle 1 Day 22 were excluded from this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E7080 6 mg BID (Dose Escalation) | Maximum Tolerated Dose (MTD) | 4 mg BID |
Secondary
Anti-tumor Effect of E7080 in Combination With Carboplatin and Paclitaxel.
Time frame: At Screening, on Day 22 of every even cycle, and at discontinuation
Secondary
Pharmacokinetics and Pharmacodynamics of E7080 in Combination With Carboplatin and Paclitaxel.
Time frame: At various time points until Day 22 of Cycle 1
Secondary
To Evaluate the Safety and Tolerability of E7080 in Combination With Carboplatin and Paclitaxel.
Refer safety section for safety analysis
Time frame: Throughout the study until 30 days after last dose