A Phase 1 Study of E7090 in Subjects With Solid Tumor
Overview
- Phase
- Phase 1
- Intervention
- E7090
- Conditions
- Tumors
- Sponsor
- Eisai Co., Ltd.
- Enrollment
- 40
- Locations
- 3
- Primary Endpoint
- Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
This is a Phase 1 study of E7090 in subjects with advanced solid tumors. This study will be conducted in 2 parts:
- Part 1 will be the dose escalation portion of this study to determine the maximum tolerated dose in subjects with solid tumors, and
- Part 2 will comprise cohort expansions to further characterize the safety and tolerability of E7090 and to assess preliminary efficacy of E7090 in subjects with solid tumors characterized by genetic abnormalities in FGF/FGFR pathway.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Part 1and Part 2
- •Provide written informed consent
- •Male or female subjects age \>= 20 years at the time of informed consent
- •Subjects with a histological and/or cytological diagnosis of solid tumor
- •Subjects who failed standard therapies, or for which no appropriate treatment is available.
- •Subjects with Performance Status (PS) score of 0-1 established by Eastern Cooperative Oncology Group (ECOG)
- •Subjects who are expected to survive for 3 months or longer after starting administration of the investigational drug.
- •Inclusion Criteria: Part 2 only
- •Subjects with tumor expressing genetic abnormality in FGF/FGFR (fibroblast growth factor/ fibroblast growth factor receptor)pathway.
- •Exclusion criteria
Exclusion Criteria
- Not provided
Arms & Interventions
E7090 Arm
Oral, starting dose 1 mg once a day, dose escalation in part 1. Cycle 0 is for 7 days. For Cycle 1 and onward, each cycle is 28 days long. The Cycle 0 is set up for PK analysis of a single dose of E7090. In the following Cycle 1, subjects will be administered E7090 QD, and the PK and safety will be assessed for 28 days. One or two doses may be selected from part 1 for Part 2. E7090 will be administered continuously once a daily. Subjects can continue treatment unless they meet discontinuation criteria.
Intervention: E7090
Outcomes
Primary Outcomes
Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)
Time Frame: Cycle 0 (Cycle length= 7 days) up to Cycle 1 (Cycle length= 28 days)
DLT was graded using Common Terminology Criteria for Adverse Events version 4.03 as follows: a. febrile neutropenia, or Grade 4 neutropenia persisting for greater than or equal to (\>=) 7 days, b. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia requiring platelet transfusions, c. Grade \>=3 non-hematological toxicity, except for: clinically insignificant laboratory abnormalities, toxicity Grade less than or equal to (\<=) 2 by best supportive care; d. potentially clinically significant, new radiographic mineralization in soft tissue, kidneys, intestines, heart, lungs, or other organs; e. Hyperphosphatemia meeting either for: serum phosphate level greater than (\>) 7 milligram per deciliter (mg/dL) persisting for \>=7 days despite best treatment, serum phosphate level \>9 mg/dL despite best treatment; f. treatment interruption for \>=8 days during Cycle 0; Cycle 1 required by E7090-related toxicity, except for treatment interruption for \>=8 days for reasons other than toxicity.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: From the start of study drug administration up to 2 year 9 months
A TEAE was defined as an adverse event (AE) that emerged during the time from the first dose of study drug to 30 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. A Serious AE is any untoward medical occurrence that at any dose: resulted in death; was life threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death) required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.
Secondary Outcomes
- Part 2: Overall Survival (OS)(From the date of first dose of study drug up to 2 years and 8 months)
- Part 2: Progression- Free Survival (PFS)(From the date of first dose of study drug up to 2 years and 8 months)
- Best Overall Response (BOR)(From the date of first dose of study drug up to 2 years and 8 months)
- Part 2: Objective Response Rate (ORR)(From screening up to 2 years and 8 months)
- Part 2: Disease Control Rate (DCR)(From the date of first dose of study drug up to 2 years and 8 months)
- Cmax: Maximum Observed Plasma Concentration for E7090(Part 1: Cycle 0 Day 1: 0-72 hours post dose (Cycle 0 is 7 days); Part 2: Cycle 1 Day 1: 0-24 hours post dose; (Cycle 1 is 28 days))
- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7090(Part 1: Cycle 0 Day 1: 0-72 hours post dose (Cycle 0 is 7 days); Part 2: Cycle 1 Day 1: 0-24 hours post dose; (Cycle 1 is 28 days))
- AUC(0-24h): Area Under the Plasma Concentration-time Curve From Zero Time to 24 Hours(Part 1: Cycle 0 Day 1: 0-24 hours post dose (Cycle 0 is 7 days); Part 2: Cycle 1 Day 1: 0-24 hours post dose (Cycle 1 is 28 days))
- Part 1: CL/F: Apparent Total Clearance for E7090(Part 1: Cycle 0 Day 1: 0-72 hours post dose (Cycle 0 is 7 days))