Clinical Trials /

A Study of E7130 in Participants With Solid Tumors

NCT03444701

Description:

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

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Adenocarcinoma
  • Colorectal Adenocarcinoma
  • Gastric Adenocarcinoma
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of E7130 in Participants With Solid Tumors
  • Official Title: A Phase 1 Study of E7130 in Subjects With Solid Tumor

Clinical Trial IDs

  • ORG STUDY ID: E7130-J081-101
  • NCT ID: NCT03444701

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
E7130E7130 (2-Week Regimen)
E7130E7130 (3-Week Regimen)

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
E7130 (2-Week Regimen)ExperimentalPart 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, additional participants will be enrolled to explore participant's optimal biologic dose (OBD). Part 2: Participants with Her2-negative breast cancer and other solid tumors 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.
  • E7130
E7130 (3-Week Regimen)ExperimentalPart 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, additional participants will be enrolled to explore participant's OBD. Part 2: Participants with Her2-negative breast cancer and other solid tumors 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.
  • E7130

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 those rules

          -  Participants age ≥ 20 years at the time of informed consent

          -  Participants with a histological and/or cytological diagnosis of solid tumor who
             failed standard therapies, or for which no appropriate treatment is available

          -  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.

          -  (Part 1 only in some of additional participants to explore candidate optimal biologic
             dose) Participants agree to be hospitalized between Cycle 1 Day 1 (C1D1) and C1D8 at
             least so that plasma, urine, and feces samples for pharmacokinetic analysis could be
             submitted.

        Inclusion Criteria (Part 2 only):

        - Measurable disease meeting the criteria.

        Inclusion Criteria (Part 2: Her2-negative breast cancer cohort only):

          -  Histologically or cytologically confirmed adenocarcinoma of Her2-negative breast
             cancer

          -  Female participants who had received at least an anthracycline and/or taxane treatment
             for the neoadjuvant/adjuvant or chemotherapy for refractory or relapse breast cancer
             and progressed radiographically

        Inclusion Criteria (Part 2: Other solid tumors cohort only):

          -  Any refractory or relapse solid tumor types as follows:

               1. Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of
                  head and neck (oropharynx, hypopharynx, larynx)

               2. Histologically or cytologically confirmed diagnosis of other tumor (e.g., gastric
                  or gastro-esophageal adenocarcinoma, and colon/rectum adenocarcinoma)

                  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.

        Exclusion Criteria (Part 2 only):

        - Previous treatment with halicondrin B or -like compound.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Number of participants assigned to the every 2 weeks regimen with dose-limiting toxicities (DLTs)
Time Frame:Cycle 1 (28 days)
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure:Part 1: Maximum Tolerated Dose (MTD) of E7130
Time Frame: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])
Safety Issue:
Description: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.
Measure:Part 1 and Part 2: Maximum observed plasma concentration (Cmax) of E7130
Time Frame: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)
Safety Issue:
Description:Cmax is the maximum observed concentration of E7130 after administration of the drug.
Measure:Part 1 and Part 2: Time to reach maximum plasma concentration (Tmax) of E7130
Time Frame: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)
Safety Issue:
Description:Tmax is the time at which the highest drug concentration occurs.
Measure:Part 1 and Part 2: Area under the plasma concentration time curve (AUC) from time 0 to 24 hours postdose
Time Frame: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)
Safety Issue:
Description:
Measure:Part 1 and Part 2: Area under the plasma concentration time curve (AUC) from time 0 to infinity
Time Frame: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)
Safety Issue:
Description:
Measure:Part 1 and Part 2: Apparent terminal elimination phase half-life (t1/2) of E7130
Time Frame: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)
Safety Issue:
Description:
Measure:Part 1 and Part 2: Total clearance of E7130
Time Frame: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)
Safety Issue:
Description:
Measure:Part 1 and Part 2: Apparent volume of distribution (Vd)
Time Frame: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)
Safety Issue:
Description:
Measure:Part 1 and Part 2: Recommended dose for future studies
Time Frame:Up to 46.5 months
Safety Issue:
Description: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.
Measure:Part 1 and Part 2: Number of participants with advanced solid tumors with anti-tumor activity
Time Frame:Up to 46.5 months
Safety Issue:
Description:
Measure:Part 1 and Part 2: Best Overall Response (BOR)
Time Frame:Up to 46.5 months
Safety Issue:
Description: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.
Measure:Part 1 and Part 2: Objective Response Rate (ORR)
Time Frame:Up to 46.5 months
Safety Issue:
Description:The ORR is defined as the percentage of participants with a BOR of CR or PR.
Measure:Part 1 and Part 2: Disease Control Rate (DCR)
Time Frame:Up to 46.5 months
Safety Issue:
Description:DCR is defined as the percentage of participants with a BOR of CR, PR, or SD.
Measure:Part 1 and Part 2: Clinical Benefit Rate (CBR)
Time Frame:Up to 46.5 months
Safety Issue:
Description:The CBR is defined as the percentage of participants with a BOR of CR, PR, or durable SD (duration of SD ≥23 weeks).
Measure:Part 2: Progression-free survival (PFS)
Time Frame:Up to 46.5 months
Safety Issue:
Description: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).
Measure:Part 2: Overall Survival (OS)
Time Frame:Up to 46.5 months
Safety Issue:
Description:OS is defined as the time from the date of the first dose to the date of death from any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eisai Co., Ltd.

Trial Keywords

  • Solid tumors
  • Her2-negative breast cancer
  • Squamous cell carcinoma of the head and neck

Last Updated

April 6, 2020