Solid Tumors
Conditions
Keywords
Solid tumors, Squamous cell carcinoma of the head and neck, Urothelial carcinoma
Brief summary
The primary objective of this study is to evaluate the tolerability and safety profile of E7130 in participants with solid tumors.
Interventions
DRUGE7130
Starting dose of 25 μg/m\^2 on Day 1 and Day 15 of Cycle 1.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a Phase 1 study of E7130 in participants with solid tumors. This study will be conducted in 2 parts (Part 1 and Part 2). Part 1 will be the dose escalation portion of this study, conducted to assess dose-limiting toxicity (DLT) and to determine the maximum tolerated dose (MTD) in participants with solid tumors. The dosage and the duration of the treatment cycle in Part 2 will be determined based on the data from Part 1. Part 2 will be comprised of cohort expansions to further characterize the safety and tolerability of E7130.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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: 1. At least 1 lesion of \>=1.0 centimeter (cm) in the longest diameter for a non-lymph node or \>=1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to response evaluation criteria in solid tumours (RECIST) 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI). 2. Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease to be deemed a target lesion.
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 * Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in the study * Scheduled for surgery during the study * Diagnosed with meningeal carcinomatosis * Participants with brain or subdural metastases are not eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of participants assigned to the every 2 weeks regimen with dose-limiting toxicities (DLTs) | 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 | 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 adverse events (AEs) | Up to approximately 83 months | — |
| Part 1 and Part 2: Number of participants with any clinically significant clinical laboratory test value | Up to approximately 83 months | Clinical significance will be determined by the Investigator. |
| Part 1 and Part 2: Number of participants with any clinically significant vital sign value | 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 | Baseline; Up to approximately 83 months | — |
| Part 1 and Part 2: Change from Baseline in body weight | Baseline; Up to approximately 83 months | — |
| Part 1 and Part 2: Number of participants with any clinically significant 12-lead electrocardiogram (ECG) value | Up to approximately 83 months | — |
| Part 1 and Part 2: Change from Baseline in the performance status (PS) score established by the Eastern Cooperative Oncology Group (ECOG) | Baseline; Up to approximately 83 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and Part 2: Best Overall Response (BOR) | Up to approximately 83 months | The BOR will be based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. BOR is defined as complete response (CR), partial response (PR), stable disease (SD), progression of disease (PD), and not evaluable (NE), where SD has to be achieved at ≥5 weeks after the first dose. |
| Part 1 and Part 2: Objective Response Rate (ORR) | Up to approximately 83 months | The ORR is defined as the percentage of participants with a BOR of CR or PR. |
| Part 1 and Part 2: Disease Control Rate (DCR) | Up to approximately 83 months | DCR is defined as the percentage of participants with a BOR of CR, PR, or SD. |
| 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]) | The MTD will be selected as the dose with the smallest difference between the target DLT rate of 25% and an estimate of DLT rate based on the posterior distribution of DLT rate for each dose. |
| Part 2: Progression-free survival (PFS) | Up to approximately 83 months | PFS is defined as the time from the date of the first dose to the first documented date of the event (disease progression or death from any cause, whichever occurs first). |
| Part 2: Overall Survival (OS) | Up to approximately 83 months | OS is defined as the time from the date of the first dose to the date of death from any cause. |
| Part 1 and Part 2: Clinical Benefit Rate (CBR) | Up to approximately 83 months | The CBR is defined as the percentage of participants with a BOR of CR, PR, or durable SD (duration of SD ≥23 weeks). |
| 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) | Cmax is the maximum observed concentration of E7130 after administration of the drug. |
| 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) | Tmax is the time at which the highest drug concentration occurs. |
| 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: 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 | The recommended dose will be determined based on the on the MTD, the optimal biologic dose, and efficacy/safety/pharmacokinetic/pharmacodynamic data in Part 1 and Part 2. |
| Part 1 and Part 2: Number of participants with advanced solid tumors with anti-tumor activity | Up to approximately 83 months | — |
Countries
Japan
Outcome results
None listed