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
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
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)

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 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) is observed, participants will be administered E7130 at the determined dose level on Days 1 and 15 of every 28-day cycle until they meet any of the criteria for discontinuation. 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 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. If a drug-related Grade 2 or higher toxicity is not observed in the initial cohort, DLTs will be evaluated in successive dose levels with single participants until such a toxicity is observed. Once the MTD is observed, participants will be administered E7130 at the determined dose level on Day 1 of every 3-week cycle until they meet any of the criteria for discontinuation. 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 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

               1. Hemoglobin ≥ 9.0 grams per deciliter

               2. Neutrophil count ≥ 1.5 x 10^3/microliter (µL)

               3. Platelet count ≥ 10 x 10^4/µL

               4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) in the facility

               5. Alanine aminotransferase and aspartate aminotransferase ≤ 3.0 x ULN in the
                  facility

               6. Serum creatinine ≤ 1.5 x ULN in the facility

          -  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 will be as follows:

             a. Anticancer therapy i. Antibody and other study drugs: > 4 weeks (however, in the
             case where the half-life of other study drugs is known and 5 × half-lives of that
             study drug is less than or equal to 4 weeks, participants can be eligible after ≥ 5 ×
             half-lives of that study drug has passed) ii. Prior chemotherapy (except
             small-molecule targeted therapy), surgical therapy, radiation therapy: > 3 weeks iii.
             Endocrine therapy, immunotherapy (except antibody drug), small-molecule targeted
             therapy: > 2 weeks b. Supportive therapies i. Blood/platelet transfusion,
             hematopoietic stimulating agent including granulocyte colony-stimulating factor
             formulation: > 2 weeks

          -  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 following criteria:

               1. At least 1 lesion of ≥1.0 centimeters (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 Tumors
                  (RECIST) 1.1 using computerized tomography/magnetic resonance imaging

               2. Lesions that have had external beam radiotherapy or locoregional therapies such
                  as radiofrequency ablation must show evidence of progressive disease based on
                  RECIST 1.1 to be deemed a target lesion

                  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:

               1. Congestive heart failure greater or equal to than New York Heart Association
                  Class II

               2. Unstable angina pectoris, myocardial infarction or stroke within 6 months before
                  of the first dose of study drug

               3. Prolongation of corrected QT interval to > 480 milliseconds (ms) (Fridericia
                  method)

               4. Arrhythmias requiring treatment

          -  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. Participants who are anti-HBs/HBcAb (+) with less than 20 international units
             per milliliter (IU/ml) hepatitis B virus-deoxyribonucleic acid (HBV-DNA) are eligible.

          -  Effusion requiring drainage (Note: participants whose symptom has been treated and
             stable for 2 weeks prior to the first administration of the study drug, are eligible)

          -  Participants whose toxicity of previous treatment has not recovered to Grade 1 or
             lower (except for alopecia)

          -  Other active malignancy (except for definitively treated melanoma in-situ, basal or
             squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the
             past 24 months prior to the first administration of the study drug

          -  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]). A separate baseline assessment is required if a negative screening pregnancy
             test was obtained more than 3 days before the first dose of study drug (breastfeeding
             participants are not eligible even if they discontinue breastfeeding).

          -  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 (as below) during the study and after study drug discontinuation (male;
             90 days, female; 60 days) Note: Condom*, contraceptive sponge**, foam**, jelly**,
             diaphragm*, intrauterine device *, or use of oral contraception* from at least 4 weeks
             before starting the study treatment (*Approved drugs or certified medical devices in
             Japan; **Non-approved drugs or certified medical devices in Japan)

          -  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, unless they have
             completed local therapy and have discontinued the use of corticosteroids for this
             indication for at least 4 weeks before starting treatment in this study. Any signs
             (e.g., radiologic) or symptoms of brain metastases must be stable for at least 4 weeks
             before starting study treatment.

        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:The following toxicities developed in Cycle 1 will be regarded as DLTs if a causal relationship with E7130 can't be ruled out: 1) Febrile neutropenia; 2) Grade 4 neutropenia that persists for more than 7 days or requires hematopoietic stimulating agents; 3) Grade 4 thrombocytopenia or thrombocytopenia that requires blood transfusion; 4) Grade 4 anemia, or anemia requiring blood transfusion; 5) Any Grade 3 non-hematological toxicity with the exception of: a) Abnormal clinical laboratory values with no clinical significance; b) Any events which can be controlled to Grade 2 or less by medical management; 6) Any Grade 4 non-hematological toxicity; 7) (In every 2 weeks regimen) Development of any toxicity that is considered to be related to E7130 and where dose skip is necessary; 8) (In every 3 weeks regimen) Development of any toxicity that is considered to be related to E7130 and where dose at Cycle 2 Day 1 is necessary to be postponed for over 14 days for recovery from the toxicities.

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], 42 days [every 3 weeks regimen])
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 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15. Tri-weekly: Cycle 1 Day 1, Cycle 2 Day 1.
Safety Issue:
Description:Cmax is the maximum observed concentration of E7130 after administration of the drug. Bi-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 minutes (min), 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion); Cycle 1 Day 15 (pre-dose; end of infusion; 168 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion). Cycle 2 Day 15 (pre-dose; end of infusion; 168 hours post-infusion). Tri-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion).
Measure:Part 1 and Part 2: Time to reach maximum plasma concentration (Tmax) of E7130
Time Frame:Bi-weekly: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15. Tri-weekly: Cycle 1 Day 1, Cycle 2 Day 1.
Safety Issue:
Description:Tmax is the time at which the highest drug concentration occurs. Bi-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 minutes (min), 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion); Cycle 1 Day 15 (pre-dose; end of infusion; 168 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion). Cycle 2 Day 15 (pre-dose; end of infusion; 168 hours post-infusion). Tri-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion).
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 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15. Tri-weekly: Cycle 1 Day 1, Cycle 2 Day 1.
Safety Issue:
Description:Bi-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 minutes (min), 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion); Cycle 1 Day 15 (pre-dose; end of infusion; 168 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion). Cycle 2 Day 15 (pre-dose; end of infusion; 168 hours post-infusion). Tri-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion).
Measure:Part 1 and Part 2: Area under the plasma concentration time curve (AUC) from time 0 to infinity
Time Frame:Bi-weekly: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15. Tri-weekly: Cycle 1 Day 1, Cycle 2 Day 1.
Safety Issue:
Description:Bi-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 minutes (min), 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion); Cycle 1 Day 15 (pre-dose; end of infusion; 168 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion). Cycle 2 Day 15 (pre-dose; end of infusion; 168 hours post-infusion). Tri-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion).
Measure:Part 1 and Part 2: Apparent terminal elimination phase half-life (t1/2) of E7130
Time Frame:Bi-weekly: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15. Tri-weekly: Cycle 1 Day 1, Cycle 2 Day 1.
Safety Issue:
Description:Bi-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 minutes (min), 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion); Cycle 1 Day 15 (pre-dose; end of infusion; 168 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion). Cycle 2 Day 15 (pre-dose; end of infusion; 168 hours post-infusion). Tri-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion).
Measure:Part 1 and Part 2: Total clearance of E7130
Time Frame:Bi-weekly: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15. Tri-weekly: Cycle 1 Day 1, Cycle 2 Day 1.
Safety Issue:
Description:Bi-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 minutes (min), 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion); Cycle 1 Day 15 (pre-dose; end of infusion; 168 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion). Cycle 2 Day 15 (pre-dose; end of infusion; 168 hours post-infusion). Tri-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion).
Measure:Part 1 and Part 2: Apparent volume of distribution (Vd)
Time Frame:Bi-weekly: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15. Tri-weekly: Cycle 1 Day 1, Cycle 2 Day 1.
Safety Issue:
Description:Bi-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 minutes (min), 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion); Cycle 1 Day 15 (pre-dose; end of infusion; 168 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, and 168 hours post-infusion). Cycle 2 Day 15 (pre-dose; end of infusion; 168 hours post-infusion). Tri-weekly: Cycle 1 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion); Cycle 2 Day 1 (pre-dose; end of infusion; 20 and 40 min, 1, 2, 4, 6, 10, 24, 48, 96, 168, and 336 hours post-infusion).
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. CR or PR in Part 1 of this study requires no confirmation of the next response at ≥4 weeks. The confirmation is mandatory in Part 2.
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). Duration of SD is defined as the time from the date of the first dose to the date of the first documentation of disease progression or death from any cause, whichever occurs first.
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

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