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A Study of E7386 in Participants With Advanced Solid Tumor Including Colorectal Cancer (CRC)

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ClinicalTrials.gov Identifier: NCT03833700
Recruitment Status : Not yet recruiting
First Posted : February 7, 2019
Last Update Posted : February 7, 2019
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Co., Ltd. )

Brief Summary:
The primary objective of this study is to assess the safety and tolerability of E7386 in participants with solid tumor including CRC.

Condition or disease Intervention/treatment Phase
Solid Neoplasms Colorectal Neoplasms Drug: E7386 Phase 1

Detailed Description:

The study will be conducted in 2 parts: dose escalation part and dose expansion part. The study will include Pre-treatment Phase, Treatment Phase, and Extension Phase (in dose expansion part only).

Eligible participants from Pre-Treatment Phase (screening period) will enter into the Treatment Phase to receive E7386. After Treatment Phase, participants will be followed in follow-up period of Extension Phase (in dose expansion part only).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase 1 Study of E7386 in Subjects With Advanced Solid Tumor Including Colorectal Cancer
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Escalation Part: E7386
Participants will receive E7386 10, 15 and 20 mg (milligram), tablets, orally, twice daily, in 28-days treatment cycle until disease progression (PD), development of unacceptable toxicity, participant's request to discontinue, withdrawal of consent, or termination of the study program. Dose escalation of E7386 will be based on the available safety data from the previous cohorts.
Drug: E7386
E7386, tablets, orally.

Experimental: Dose Expansion Part
Participants will receive E7386, tablets, orally, twice daily in 28-days treatment cycle until PD, development of unacceptable toxicity, participant's request to discontinue, withdrawal of consent, or termination of the study program. The highest dose of E7386 which is deemed tolerable in dose escalation part will be used.
Drug: E7386
E7386, tablets, orally.




Primary Outcome Measures :
  1. Number of Participants with Dose-limiting Toxicities (DLTs) [ Time Frame: Baseline up to Cycle 1 (Cycle length is equal to [=] 28 days) ]
    DLT will be defined as any of the events that are considered by the investigator to be at least possibly related to therapy with the study medication. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0).

  2. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 30 days after the last dose of study drug or before initiating post anti-cancer treatment (approximately 2 years) ]

Secondary Outcome Measures :
  1. Cmax: Maximum Observed Plasma Concentration for E7386 [ Time Frame: Cycle 1 Day 1: 0-12 hours; Cycle 1 Day 8: 0-12 hours (Cycle length=28 days) ]
  2. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7386 [ Time Frame: Cycle 1 Day 1: 0-12 hours; Cycle 1 Day 8: 0-12 hours (Cycle length=28 days) ]
  3. AUC: Area Under the Plasma Concentration Versus Time Curve for E7386 [ Time Frame: Cycle 1 Day 1: 0-12 hours; Cycle 1 Day 8: 0-12 hours (Cycle length=28 days) ]
  4. CL/F: Apparent Total Body Clearance for E7386 [ Time Frame: Cycle 1 Day 1: 0-12 hours; Cycle 1 Day 8: 0-12 hours (Cycle length=28 days) ]
  5. Vz/F: Apparent Volume of Distribution for E7386 [ Time Frame: Cycle 1 Day 1: 0-12 hours; Cycle 1 Day 8: 0-12 hours (Cycle length=28 days) ]
  6. Percentage of Participants with Best Overall Response (BOR) [ Time Frame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 2 years) ]
    BOR is defined as complete response (CR), partial response (PR), stable disease (SD), PD, and not evaluable (NE), where SD has to be achieved at greater than or equal to (>=) 7 weeks after the first dose. The BOR will be assessed by investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  7. Objective Response Rate (ORR) [ Time Frame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 2 years) ]
    The ORR is defined as the percentage of participants with a BOR of CR or PR. The ORR will be assessed by investigator based on RECIST version 1.1.

  8. Disease Control Rate (DCR) [ Time Frame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 2 years) ]
    DCR is defined as the percentage of participants with a BOR of CR, PR, or SD. The DCR will be assessed by investigator based on RECIST version 1.1.

  9. Clinical Benefit Rate (CBR) [ Time Frame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 2 years) ]
    The CBR is defined as the percentage of participants with a BOR of CR, PR, or durable SD (duration of SD >=23 weeks). The CBR will be assessed by investigator based on RECIST version 1.1.

  10. Progression-free Survival (PFS) [ Time Frame: From first dose of study drug until PD, or death from any cause, whichever occurs first (up to approximately 2 years) ]
    PFS is defined as the time from the date of the first dose to the date of the first documentation of confirmed PD or death, whichever occurs first.



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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:

  1. Participants must have any of the following tumor types:

    1. Dose Escalation Part: Participants with advanced, unresectable, or recurrent solid tumor including CRC for which no alternative standard therapy or no effective therapy exists
    2. Dose Expansion Part: Participants with advanced, unresectable, or recurrent CRC for which no alternative standard therapy or no effective therapy exists
  2. Participants with CRC must consent to biopsy
  3. Life expectancy of >=12 weeks
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
  5. All AEs due to previous anti-cancer therapy have either returned to Grade 0-1 except for alopecia and Grade 2 peripheral neuropathy (renal/bone marrow/liver function should meet the inclusion criteria)
  6. Adequate washout period before study drug administration:

    1. Chemotherapy and radiotherapy: 3 weeks or more
    2. Any therapy with antibody: 4 weeks or more
    3. Any investigational drug or device: 4 weeks or more
    4. Blood/platelet transfusion or Granulocyte-colony stimulating factor (G-CSF): 2 weeks or more
  7. Adequate renal, bone marrow, liver function, and serum mineral level
  8. At least one measurable lesion based on RECIST 1.1

Exclusion Criteria:

  1. Known to be human immunodeficiency virus (HIV) positive
  2. Active infection requiring systemic treatment
  3. Diagnosed with meningeal carcinomatosis
  4. 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 (example: radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment
  5. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
  6. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (example: nausea, diarrhea, or vomiting) that might impair the bioavailability of E7386
  7. Any of bone disease/conditions as follows;

    1. Osteoporosis with T-score < -2.5 by Dual X-ray absorptiometry (DXA) scan
    2. Beta-computed Tomography X-Ray (CTX) (urine) > 500 microgram per millimoles (mcg/mmol)∙Cr
    3. Osteomalacia
    4. Symptomatic hypercalcemia requiring bisphosphonate therapy
    5. History of any fracture within 6 months prior to starting study drug
    6. Any condition requiring orthopedic intervention
    7. In spite of bone metastases, lack of treatment with a bisphosphonate or denosumab
  8. History of active malignancy (except for original disease, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, carcinoma in-situ of the bladder or cervix, or early stage gastric/colorectal cancer) within the past 24 months prior to the first dose of study drug

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): NCT03833700


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

Sponsors and Collaborators
Eisai Co., Ltd.

Responsible Party: Eisai Co., Ltd.
ClinicalTrials.gov Identifier: NCT03833700     History of Changes
Other Study ID Numbers: E7386-J081-103
First Posted: February 7, 2019    Key Record Dates
Last Update Posted: February 7, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eisai Inc. ( Eisai Co., Ltd. ):
Solid Tumor
Colorectal Cancer
E7386

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases