This study will be conducted to assess the safety and tolerability of E7386 in participants with solid tumor including CRC.
The study will be conducted in 3 parts: dose escalation part, expansion part 1 and expansion part 2. The study will consist of Primary Assessment Phase and Continuation Phase. Primary Assessment Phase will include Pre-treatment Phase, Treatment Phase and Extension Phase (in expansion parts only). After Treatment Phase, participants will be followed in follow-up period of Extension Phase (in expansion parts only). All participants who are still on study drug at the time of data cutoff date for the planned primary analysis will enter the Continuation phase and continue to receive E7386.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
E7386 doses.
Eisai Trial Site#7
Nagoya, Aichi-ken, Japan
Eisai Trial Site #2
Kashiwa, Chiba, Japan
Eisai Trial Site #5
Sapporo, Hokkaido, Japan
Eisai Trial Site#8
Sendai, Miyagi, Japan
Number of Participants with Dose-limiting Toxicities (DLTs)
DLT will be defined as any of the events that are considered by the investigator to be at least possibly related to therapy with the study medication. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0).
Time frame: Baseline up to Cycle 1 (Cycle length is equal to [=] 28 days)
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 30 days after the last dose of study drug or before initiating post anti-cancer treatment (approximately 6 years)
Cmax: Maximum Observed Plasma Concentration for E7386
Time frame: Dose escalation Part, Cycles 1 to 6: Up to Day 8; Dose Expansion Part 1 and 2, Cycles 1 and 2: Up to Day 8 (Cycle length=28 days)
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7386
Time frame: Dose escalation Part, Cycles 1 to 6: Up to Day 8; Dose Expansion Part 1 and 2, Cycles 1 and 2: Up to Day 8 (Cycle length=28 days)
AUC: Area Under the Plasma Concentration Versus Time Curve for E7386
Time frame: Dose escalation Part, Cycles 1 to 6: Up to Day 8; Dose Expansion Part 1 and 2, Cycles 1 and 2: Up to Day 8 (Cycle length=28 days)
CL/F: Apparent Total Body Clearance for E7386
Time frame: Dose escalation Part, Cycles 1 to 6: Up to Day 8; Dose Expansion Part 1 and 2, Cycles 1 and 2: Up to Day 8 (Cycle length=28 days)
Vz/F: Apparent Volume of Distribution for E7386
Time frame: Dose escalation Part, Cycles 1 to 6: Up to Day 8; Dose Expansion Part 1 and 2, Cycles 1 and 2: Up to Day 8 (Cycle length=28 days)
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Eisai Trial Site #3
Nagaizumi-cho, Shizuoka, Japan
Eisai Trial Site #1
Chuo Ku, Tokyo, Japan
Eisai Trial Site #4
Fukuoka, Japan
Eisai Trial Site#6
Osaka, Japan
Objective Response Rate (ORR)
The ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). The ORR will be assessed by investigator based on RECIST version 1.1.
Time frame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 6 years)
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a BOR of CR, PR, or stable disease (SD). The DCR will be assessed by investigator based on RECIST version 1.1.
Time frame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 6 years)
Clinical Benefit Rate (CBR)
The CBR is defined as the percentage of participants with a BOR of CR, PR, or durable SD. The CBR will be assessed by investigator based on RECIST version 1.1.
Time frame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 6 years)
Progression-free Survival (PFS)
PFS is defined as the time from the date of the first dose to the date of the first documentation of confirmed PD or death, whichever occurs first.
Time frame: From first dose of study drug until PD, or death from any cause, whichever occurs first (up to approximately 6 years)
Duration of Response (DOR)
DOR is defined as the time from the first date of documented CR or PR to the date of PD or death, whichever occurs first. It will be calculated for participants whose BOR is CR or PR. DOR will be assessed according to RECIST version 1.1.
Time frame: From the date of first documented CR or PR until first documentation of PD or death (up to approximately 6 years)
Overall Survival (OS)
OS is defined as the time from the date of first dose to the date of death.
Time frame: From first dose of study drug until date of death (up to approximately 6 years)