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A Study of E7130 in Participants With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03444701
Recruitment Status : Recruiting
First Posted : February 23, 2018
Last Update Posted : April 6, 2020
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Co., Ltd. )

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

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: E7130 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of E7130 in Subjects With Solid Tumor
Actual Study Start Date : February 5, 2018
Estimated Primary Completion Date : March 1, 2023
Estimated Study Completion Date : March 1, 2023

Arm Intervention/treatment
Experimental: E7130 (2-Week Regimen)
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, 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.
Drug: E7130
Starting dose of 25 μg/m^2 on Day 1 and Day 15 of Cycle 1

Experimental: E7130 (3-Week Regimen)
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, 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.
Drug: E7130
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




Primary Outcome Measures :
  1. Part 1: Number of participants assigned to the every 2 weeks regimen with dose-limiting toxicities (DLTs) [ Time Frame: 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).

  2. Part 1: Number of participants assigned to the every 3 weeks regimen with DLTs [ Time Frame: Cycle 1 (21 days) ]
    DLTs are defined as study drug related AEs. Toxicity will be evaluated according to NCI CTCAE 4.03.

  3. Part 1 and Part 2: Number of participants with adverse events (AEs) [ Time Frame: Up to 46.5 months ]
  4. Part 1 and Part 2: Number of participants with any clinically significant clinical laboratory test value [ Time Frame: Up to 46.5 months ]
    Clinical significance will be determined by the Investigator.

  5. Part 1 and Part 2: Number of participants with any clinically significant vital sign value [ Time Frame: Up to 46.5 months ]
    Clinical significance will be determined by the Investigator.

  6. Part 1 and Part 2: Change from Baseline in arterial oxygen saturation [ Time Frame: Baseline; Up to 46.5 months ]
  7. Part 1 and Part 2: Change from Baseline in body weight [ Time Frame: Baseline; Up to 46.5 months ]
  8. Part 1 and Part 2: Number of participants with any clinically significant 12-lead electrocardiogram (ECG) value [ Time Frame: Up to 46.5 months ]
  9. Part 1 and Part 2: Change from Baseline in the performance status (PS) score established by the Eastern Cooperative Oncology Group (ECOG) [ Time Frame: Baseline; Up to 46.5 months ]

Secondary Outcome Measures :
  1. 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]) ]
    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.

  2. 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) ]
    Cmax is the maximum observed concentration of E7130 after administration of the drug.

  3. 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) ]
    Tmax is the time at which the highest drug concentration occurs.

  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. 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) ]
  8. 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) ]
  9. Part 1 and Part 2: Recommended dose for future studies [ Time Frame: Up to 46.5 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.

  10. Part 1 and Part 2: Number of participants with advanced solid tumors with anti-tumor activity [ Time Frame: Up to 46.5 months ]
  11. Part 1 and Part 2: Best Overall Response (BOR) [ Time Frame: Up to 46.5 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.

  12. Part 1 and Part 2: Objective Response Rate (ORR) [ Time Frame: Up to 46.5 months ]
    The ORR is defined as the percentage of participants with a BOR of CR or PR.

  13. Part 1 and Part 2: Disease Control Rate (DCR) [ Time Frame: Up to 46.5 months ]
    DCR is defined as the percentage of participants with a BOR of CR, PR, or SD.

  14. Part 1 and Part 2: Clinical Benefit Rate (CBR) [ Time Frame: Up to 46.5 months ]
    The CBR is defined as the percentage of participants with a BOR of CR, PR, or durable SD (duration of SD ≥23 weeks).

  15. Part 2: Progression-free survival (PFS) [ Time Frame: Up to 46.5 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).

  16. Part 2: Overall Survival (OS) [ Time Frame: Up to 46.5 months ]
    OS is defined as the time from the date of the first dose to the date of death from any cause.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03444701


Contacts
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Contact: Inquiry Service eisai-chiken_hotline@hhc.eisai.co.jp

Locations
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Japan
Eisai Trial Site 1 Recruiting
Kashiwa, Chiba, Japan
Eisai Trial Site 2 Recruiting
Kotoku, Tokyo, Japan
Sponsors and Collaborators
Eisai Co., Ltd.

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Responsible Party: Eisai Co., Ltd.
ClinicalTrials.gov Identifier: NCT03444701    
Other Study ID Numbers: E7130-J081-101
First Posted: February 23, 2018    Key Record Dates
Last Update Posted: April 6, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Eisai Inc. ( Eisai Co., Ltd. ):
Solid tumors
Her2-negative breast cancer
Squamous cell carcinoma of the head and neck
Additional relevant MeSH terms:
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Neoplasms