A Study of E7130 in Participants With Solid Tumors

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the tolerability and safety profile of E7130 in participants with advanced solid tumors.

Official Title
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A Phase 1 Study of E7130 in Subjects With Solid Tumor

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: E7130
* Drug: E7130


Participation Criteria
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Eligibility Criteria
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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 those rules Participants age 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 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 agree to submit blood samples prior and during study treatment for progressive disease markers. Inclusion Criteria (Part 2 only): Measurable disease meeting the following criteria: 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). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion. Exclusion Criteria: Medical history of clinically significant cardiovascular impairment 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), 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) 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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is a Phase 1 study of E7130 in participants with advanced 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E7130 (2-Week Regimen)<br>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. | Drug: E7130<br>* Starting dose of 25 μg/m^2 on Day 1 and Day 15 of Cycle 1.<br>|
| Experimental: E7130 (3-Week Regimen)<br>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. | Drug: E7130<br>* Starting dose is lower than one at which the first DLT was observed in the 2-week regimen administered on Day 1 of Cycle 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of participants assigned to the every 2 weeks regimen with dose-limiting toxicities (DLTs) | 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). | Cycle 1 (28 days) | 
| Part 1: Number of participants assigned to the every 3 weeks regimen with DLTs | DLTs are defined as study drug related AEs. Toxicity will be evaluated according to NCI CTCAE 4.03. | Cycle 1 (21 days) | 
| Part 1 and Part 2: Number of participants with adverse events (AEs) |  | Up to approximately 93 months | 
| Part 1 and Part 2: Number of participants with any clinically significant clinical laboratory test value | Clinical significance will be determined by the Investigator. | Up to approximately 93 months | 
| Part 1 and Part 2: Number of participants with any clinically significant vital sign value | Clinical significance will be determined by the Investigator. | Up to approximately 93 months | 
| Part 1 and Part 2: Change from Baseline in arterial oxygen saturation |  | Baseline; Up to approximately 93 months | 
| Part 1 and Part 2: Change from Baseline in body weight |  | Baseline; Up to approximately 93 months | 
| Part 1 and Part 2: Number of participants with any clinically significant 12-lead electrocardiogram (ECG) value |  | Up to approximately 93 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 93 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Maximum Tolerated Dose (MTD) of E7130 | 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. | 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 and Part 2: Maximum observed plasma concentration (Cmax) of E7130 | Cmax is the maximum observed concentration of E7130 after administration of the drug. | Bi-weekly: Cycle (C)1-2 Day (D)1, 15: 0-168 hours (h) post-infusion; C3-4 D1, 8, 15 and C5-8 Day 1: 0-end of infusion (each C=28 days); Tri-weekly: C1-2 D1: 0-336 h post-infusion, C3-C4 D1, D8, D15 and C5-8 D1 and D15: 0-end of infusion (each C=21 days) | 
| Part 1 and Part 2: Time to reach maximum plasma concentration (Tmax) of E7130 | Tmax is the time at which the highest drug concentration occurs. | Bi-weekly: Cycle (C)1-2 Day (D)1, 15: 0-168 hours (h) post-infusion; C3-4 D1, 8, 15 and C5-8 Day 1: 0-end of infusion (each C=28 days); Tri-weekly: C1-2 D1: 0-336 h post-infusion, C3-C4 D1, D8, D15 and C5-8 D1 and D15: 0-end of infusion (each C=21 days) | 
| Part 1 and Part 2: Area under the plasma concentration time curve (AUC) from time 0 to 24 hours postdose |  | Bi-weekly: Cycle (C)1-2 Day (D)1, 15: 0-168 hours (h) post-infusion; C3-4 D1, 8, 15 and C5-8 Day 1: 0-end of infusion (each C=28 days); Tri-weekly: C1-2 D1: 0-336 h post-infusion, C3-C4 D1, D8, D15 and C5-8 D1 and D15: 0-end of infusion (each C=21 days) | 
| Part 1 and Part 2: Area under the plasma concentration time curve (AUC) from time 0 to infinity |  | Bi-weekly: Cycle (C)1-2 Day (D)1, 15: 0-168 hours (h) post-infusion; C3-4 D1, 8, 15 and C5-8 Day 1: 0-end of infusion (each C=28 days); Tri-weekly: C1-2 D1: 0-336 h post-infusion, C3-C4 D1, D8, D15 and C5-8 D1 and D15: 0-end of infusion (each C=21 days) | 
| Part 1 and Part 2: Apparent terminal elimination phase half-life (t1/2) of E7130 |  | Bi-weekly: Cycle (C)1-2 Day (D)1, 15: 0-168 hours (h) post-infusion; C3-4 D1, 8, 15 and C5-8 Day 1: 0-end of infusion (each C=28 days); Tri-weekly: C1-2 D1: 0-336 h post-infusion, C3-C4 D1, D8, D15 and C5-8 D1 and D15: 0-end of infusion (each C=21 days) | 
| Part 1 and Part 2: Total clearance of E7130 |  | Bi-weekly: Cycle (C)1-2 Day (D)1, 15: 0-168 hours (h) post-infusion; C3-4 D1, 8, 15 and C5-8 Day 1: 0-end of infusion (each C=28 days); Tri-weekly: C1-2 D1: 0-336 h post-infusion, C3-C4 D1, D8, D15 and C5-8 D1 and D15: 0-end of infusion (each C=21 days) | 
| Part 1 and Part 2: Apparent volume of distribution (Vd) |  | Bi-weekly: Cycle (C)1-2 Day (D)1, 15: 0-168 hours (h) post-infusion; C3-4 D1, 8, 15 and C5-8 Day 1: 0-end of infusion (each C=28 days); Tri-weekly: C1-2 D1: 0-336 h post-infusion, C3-C4 D1, D8, D15 and C5-8 D1 and D15: 0-end of infusion (each C=21 days) | 
| Part 1 and Part 2: Recommended dose for future studies | 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. | Up to approximately 93 months | 
| Part 1 and Part 2: Number of participants with advanced solid tumors with anti-tumor activity |  | Up to approximately 93 months | 
| Part 1 and Part 2: Best Overall Response (BOR) | 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. | Up to approximately 93 months | 
| Part 1 and Part 2: Objective Response Rate (ORR) | The ORR is defined as the percentage of participants with a BOR of CR or PR. | Up to approximately 93 months | 
| Part 1 and Part 2: Disease Control Rate (DCR) | DCR is defined as the percentage of participants with a BOR of CR, PR, or SD. | Up to approximately 93 months | 
| Part 1 and Part 2: Clinical Benefit Rate (CBR) | The CBR is defined as the percentage of participants with a BOR of CR, PR, or durable SD (duration of SD ≥23 weeks). | Up to approximately 93 months | 
| Part 2: Progression-free survival (PFS) | 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). | Up to approximately 93 months | 
| Part 2: Overall Survival (OS) | OS is defined as the time from the date of the first dose to the date of death from any cause. | Up to approximately 93 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumors, Squamous cell carcinoma of the head and neck, Urothelial carcinoma