A Phase 1 Study of E7130 in Subjects With Solid Tumor
Overview
- Phase
- Phase 1
- Intervention
- E7130
- Conditions
- Solid Tumors
- Sponsor
- Eisai Co., Ltd.
- Enrollment
- 62
- Locations
- 9
- Primary Endpoint
- Part 1 and Part 2: Change from Baseline in the performance status (PS) score established by the Eastern Cooperative Oncology Group (ECOG)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The primary objective of this study is to evaluate the tolerability and safety profile of E7130 in participants with solid tumors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants who have provided voluntary written consent for participation in this clinical study
- •Participants to whom the rules for complying with this clinical study have been adequately explained, and who intend to and can comply with these rules
- •Participants aged greater than or equal to (\>=) 20 years at the time of informed consent
- •Participants with adequate function of major organs
- •Participants with Performance Status score of 0 to 1 established by the Eastern Cooperative Oncology Group (ECOG)
- •Participants who are expected to survive for 3 months or longer after starting administration of the investigational drug
- •Washout period required from the end of prior treatment to the first administration of study drug
- •Participants who agree to submit blood samples prior and during study treatment for progressive disease (PD) markers.
- •Inclusion Criteria (Part 2 only):
- •Measurable disease meeting the following criteria:
Exclusion Criteria
- •Medical history of clinically significant cardiovascular impairment
- •Serious concomitant systemic infection requiring medical treatment (including bacterial infection and fungal infection)
- •Participants who test positive for human immunodeficiency virus (HIV antibody)
- •Active viral hepatitis (B or C) as demonstrated by positive serology or requiring treatment hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibody (anti-HBs)/hepatitis B core antibody (HBcAb) and anti-hepatitis C virus (HCV) antibody test.
- •Effusion requiring drainage
- •Participants whose toxicity of previous treatment has not recovered to Grade 1 or lower (except for alopecia and hemoglobin)
- •Other active malignancy
- •Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin \[ß-hCG\] or human chorionic gonadotropin \[hCG\]).
- •Women of childbearing potential or men of impregnate potential who don't agree that both the participant and his/her partner will use a medically effective method for contraception during the study and after study drug discontinuation (male; 90 days, female; 60 days)
- •Known intolerance to the study drug or any of the excipients
Arms & Interventions
E7130 (2-Week Regimen)
Part 1 (Cycle 1; 28 days): The first cohort of 3 participants will receive 25 micrograms per meters squared (μg/m\^2) of E7130, on Day 1 and Day 15 as an intravenous infusion. If a drug-related Grade 2 or higher toxicity excluding clinically insignificant events is not observed in the initial cohort, dose-limiting toxicities (DLTs) will be evaluated in successive dose levels with single participants until such a toxicity is observed. Once the maximum tolerated dose (MTD) will be determined. Part 2: Participants with squamous cell carcinoma of the head and neck and urothelial carcinoma will be evaluated at the dose level determined in Part 1 in a 2-week or in a 3-week regimen based on the evaluations in Part 1.
Intervention: E7130
E7130 (3-Week Regimen)
Part 1 (Cycle 1; 21 days): On Day 1, participants will receive E7130 at (-1) a lower dose than the dose at which the first DLT was observed in the 2-week regimen. Once the MTD will be determined. Part 2: Participants with squamous cell carcinoma of the head and neck and urothelial carcinoma will be evaluated at the dose level determined in Part 1 in a 3-week or in a 2-week regimen based on the evaluations in Part 1.
Intervention: E7130
Outcomes
Primary Outcomes
Part 1 and Part 2: Change from Baseline in the performance status (PS) score established by the Eastern Cooperative Oncology Group (ECOG)
Time Frame: Baseline; Up to approximately 83 months
Part 1: Number of participants assigned to the every 2 weeks regimen with dose-limiting toxicities (DLTs)
Time Frame: Cycle 1 (28 days)
DLTs are defined as study drug related adverse events (AEs). Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE 4.03).
Part 1: Number of participants assigned to the every 3 weeks regimen with DLTs
Time Frame: Cycle 1 (21 days)
DLTs are defined as study drug related AEs. Toxicity will be evaluated according to NCI CTCAE 4.03.
Part 1 and Part 2: Number of participants with any clinically significant vital sign value
Time Frame: Up to approximately 83 months
Clinical significance will be determined by the Investigator.
Part 1 and Part 2: Change from Baseline in body weight
Time Frame: Baseline; Up to approximately 83 months
Part 1 and Part 2: Number of participants with adverse events (AEs)
Time Frame: Up to approximately 83 months
Part 1 and Part 2: Number of participants with any clinically significant clinical laboratory test value
Time Frame: Up to approximately 83 months
Clinical significance will be determined by the Investigator.
Part 1 and Part 2: Change from Baseline in arterial oxygen saturation
Time Frame: Baseline; Up to approximately 83 months
Part 1 and Part 2: Number of participants with any clinically significant 12-lead electrocardiogram (ECG) value
Time Frame: Up to approximately 83 months
Secondary Outcomes
- Part 1: Maximum Tolerated Dose (MTD) of E7130(Cycle 1 and Cycle 2 (56 days [every 2 weeks regimen] [each Cycle length = 28 days], 42 days [every 3 weeks regimen] [each Cycle length = 21 days]))
- Part 1: Area under the plasma concentration time curve (AUC) from time 0 to infinity(Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days))
- Part 1: Maximum observed plasma concentration (Cmax) of E7130(Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days))
- Part 1: Time to reach maximum plasma concentration (Tmax) of E7130(Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days))
- Part 1: Terminal elimination phase half-life (t1/2) of E7130(Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days))
- Part 1: Total clearance of E7130(Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days))
- Part 1: Volume of distribution (Vd)(Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days))
- Part 1 and Part 2: Recommended dose for future studies(Up to approximately 83 months)
- Part 1 and Part 2: Number of participants with advanced solid tumors with anti-tumor activity(Up to approximately 83 months)
- Part 1 and Part 2: Clinical Benefit Rate (CBR)(Up to approximately 83 months)
- Part 2: Progression-free survival (PFS)(Up to approximately 83 months)
- Part 2: Overall Survival (OS)(Up to approximately 83 months)
- Part 1 and Part 2: Best Overall Response (BOR)(Up to approximately 83 months)
- Part 1 and Part 2: Objective Response Rate (ORR)(Up to approximately 83 months)
- Part 1 and Part 2: Disease Control Rate (DCR)(Up to approximately 83 months)