Clinical trial NCT03444701: A Study of E7130 in Participants With Solid Tumors
Official title: A Phase 1 Study of E7130 in Subjects With Solid Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Solid tumors
Squamous cell carcinoma of the head and neck
Urothelial carcinoma
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2018-02-23
Enrollment: 62
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the tolerability and safety profile of E7130 in participants with solid tumors.


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:

  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.

Primary outcomes:
measure: Part 1: Number of participants assigned to the every 2 weeks regimen with dose-limiting toxicities (DLTs)
timeFrame: Cycle 1 (28 days)
measure: Part 1: Number of participants assigned to the every 3 weeks regimen with DLTs
timeFrame: Cycle 1 (21 days)
measure: Part 1 and Part 2: Number of participants with adverse events (AEs)
timeFrame: Up to approximately 83 months
measure: Part 1 and Part 2: Number of participants with any clinically significant clinical laboratory test value
timeFrame: Up to approximately 83 months
measure: Part 1 and Part 2: Number of participants with any clinically significant vital sign value
timeFrame: Up to approximately 83 months
measure: Part 1 and Part 2: Change from Baseline in arterial oxygen saturation
timeFrame: Baseline; Up to approximately 83 months
measure: Part 1 and Part 2: Change from Baseline in body weight
timeFrame: Baseline; Up to approximately 83 months
measure: Part 1 and Part 2: Number of participants with any clinically significant 12-lead electrocardiogram (ECG) value
timeFrame: Up to approximately 83 months
measure: Part 1 and Part 2: Change from Baseline in the performance status (PS) score established by the Eastern Cooperative Oncology Group (ECOG)
timeFrame: Baseline; Up to approximately 83 months
Secondary outcomes:
measure: Part 1: Maximum Tolerated Dose (MTD) of E7130
timeFrame: 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])
measure: Part 1: Maximum observed plasma concentration (Cmax) of E7130
timeFrame: 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)
measure: Part 1: Time to reach maximum plasma concentration (Tmax) of E7130
timeFrame: 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)
measure: Part 1: Area under the plasma concentration time curve (AUC) from time 0 to infinity
timeFrame: 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)
measure: Part 1: Terminal elimination phase half-life (t1/2) of E7130
timeFrame: 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)
measure: Part 1: Total clearance of E7130
timeFrame: 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)
measure: Part 1: Volume of distribution (Vd)
timeFrame: 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)
measure: Part 1 and Part 2: Recommended dose for future studies
timeFrame: Up to approximately 83 months
measure: Part 1 and Part 2: Number of participants with advanced solid tumors with anti-tumor activity
timeFrame: Up to approximately 83 months
measure: Part 1 and Part 2: Best Overall Response (BOR)
timeFrame: Up to approximately 83 months
measure: Part 1 and Part 2: Objective Response Rate (ORR)
timeFrame: Up to approximately 83 months
measure: Part 1 and Part 2: Disease Control Rate (DCR)
timeFrame: Up to approximately 83 months
measure: Part 1 and Part 2: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 83 months
measure: Part 2: Progression-free survival (PFS)
timeFrame: Up to approximately 83 months
measure: Part 2: Overall Survival (OS)
timeFrame: Up to approximately 83 months
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Eisai Trial Site 9
state: Aichi
city: Kashiwa
country: Japan
facility: Eisai Trial Site 1
state: Chiba
city: Kashiwa
country: Japan
facility: Eisai Trial Site 6
state: Chiba
city: Sapporo
country: Japan
facility: Eisai Trial Site 8
state: Hokkaido
city: Sendai
country: Japan
facility: Eisai Trial Site 4
state: Miyagi
city: Chuo-ku
country: Japan
facility: Eisai Trial Site 5
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Eisai Trial Site 7
state: Tokyo
city: Chuo-ku
country: Japan
facility: Eisai Trial Site 3
state: Tokyo
city: Koto-ku
country: Japan
facility: Eisai Trial Site 2
state: Tokyo
Study officials:
References: