Clinical Trials /

Study of E7046 in Subjects With Selected Advanced Malignancies

NCT02540291

Description:

This is an open label, multicenter, Phase 1 study of E7046 to assess the safety and tolerability of E7046 and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of E7046.

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Study of <span class="go-doc-concept go-doc-intervention">E7046</span> in Subjects With Selected Advanced Malignancies

Title

  • Brief Title: Study of E7046 in Subjects With Selected Advanced Malignancies
  • Official Title: An Open-Label Multicenter Phase 1 Study of E7046 in Subjects With Selected Advanced Malignancies
  • Clinical Trial IDs

    NCT ID: NCT02540291

    ORG ID: E7046-G000-101

    Trial Conditions

    Tumors

    Trial Interventions

    Drug Synonyms Arms
    E7046 E7046

    Trial Purpose

    This is an open label, multicenter, Phase 1 study of E7046 to assess the safety and
    tolerability of E7046 and to determine the maximum tolerated dose (MTD) and/or the
    recommended Phase 2 dose (RP2D) of E7046.

    Detailed Description

    The study will be conducted in 2 parts: a dose escalation part to determine the MTD and/or
    RP2D of E7046, and a cohort expansion part with 6 to 16 participants to better characterize
    safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) at the RP2D. In the dose
    escalation part, increasing doses of E7046 will be administered to cohorts of 6
    participants, at dose levels ranging from 125 mg to 750 mg.

    Trial Arms

    Name Type Description Interventions
    E7046 Experimental Participants with tumor types that harbor high levels of myeloid infiltrate based on the Cancer Genome Atlas (TCGA). E7046

    Eligibility Criteria

    Inclusion Criteria:

    1. Age greater than or equal to 18 years

    2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

    3. Life expectancy greater than or equal to 12 weeks

    4. Participants must have any of the following tumor types, confirmed by available
    pathology records or current biopsy, that is advanced, nonresectable, or recurrent
    and progressing since last antitumor therapy, and for which no alternative standard
    therapy exists: pancreatic adenocarcinoma, renal clear cell carcinoma, SCCHN
    (squamous cell carcinoma of head and neck), NSCLC (non-small cell lung cancer),
    colorectal cancer (CRC), hepatocellular carcinoma (HCC), ovarian serous epithelial
    cancer, bladder transitional cancer, cervical cancer, and triple-negative breast
    cancer

    5. Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given
    to control the cancer) must have been completed at least 4 weeks before study drug
    administration, and all adverse events (AEs) have either returned to baseline or
    stabilized.

    6. Prior definitive radiation therapy must have been completed at least 6 weeks before
    study drug administration and the irradiated lesions should show evidence of
    progression if they are intended to be considered target lesions. Prior palliative
    radiotherapy must be completed at least 2 weeks before study drug administration. The
    radiotherapy related side effects must have resolved before the study entry. No
    radiopharmaceuticals (strontium, samarium) will be allowed within 8 weeks before
    study drug administration.

    7. Participants must have accessible tumors and consent to repeated biopsy for
    performance of correlative tissue studies

    8. Must have at least one measurable lesion per irRECIST (immune-related Response
    Evaluation Criteria Criteria in Solid Tumors):

    - At least 1 lesion of greater than or equal to 10 mm in the longest diameter for
    a non-lymph node or greater than or equal to 15 mm in the short-axis diameter
    for a lymph node that is serially measurable according to irRECIST using
    computerized tomography/magnetic resonance imaging (CT/MRI)

    - Lesions that have had definitive external beam radiotherapy or locoregional
    therapies such as radiofrequency (RF) ablation or brachytherapy must show
    evidence of progressive disease to be deemed a target lesion

    9. Prior treated brain or meningeal metastases must be without evidence of progression
    (confirmed by MRI) for at least 8 weeks and off immunosuppressive doses of systemic
    steroids (greater than 10 mg/day prednisone or equivalent) for at least 4 weeks
    before study drug administration

    10. Immunosuppressive doses of systemic medications, such as steroids or absorbed topical
    steroids (doses greater than 7.5 to 10 mg/day prednisone or equivalent) must be
    discontinued at least 2 weeks before study drug administration.

    11. Participants with prior Hepatitis B or C are eligible on the condition that
    participants have adequate liver function as defined by Inclusion Criterion number 16
    and Exclusion Criterion number 5

    12. Left ventricular ejection fraction (LVEF) greater than 50% on echocardiography or
    multiple gated acquisition (MUGA) scan

    13. Adequate renal function defined as serum creatinine less than 1.5 X ULN (upper limit
    of normal) or use SI units or calculated creatinine clearance greater than or equal
    to 50 mL/min per the Cockcroft and Gault formula

    14. Adequate bone marrow function:

    - Absolute neutrophil count (ANC) greater than or equal to 1500/mm3 (greater than
    or equal to 1.5 X 103/ul)

    - Platelets greater than or equal to 100,000/mm3 (greater than or equal to 100 X
    109/L)

    - Hemoglobin greater than or equal to 9.0 g/dL

    15. Adequate liver function:

    - Total bilirubin less than or equal to 1.5 X ULN except for unconjugated
    hyperbilirubinemia of Gilbert's syndrome

    - Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate
    aminotransferase (AST) less than or equal to 3 X ULN (less than or equal to 5 X
    ULN if participant has liver metastases). If alkaline phosphatase is greater
    than 3 X ULN (in absence of liver metastases) or greater than 5 X ULN (in
    presence of liver metastases) AND the participant also is known to have bone
    metastases, the liver specific alkaline phosphatase must be separated from the
    total and used to assess the liver function instead of total alkaline
    phosphatase

    16. Adequate blood coagulation function as evidenced by an International Normalized Ratio
    (INR) less than or equal to 1.5

    17. Willing and able to comply with all aspects of the protocol

    18. Provide written informed consent prior to any study specific screening procedures

    19. Females must not be lactating or pregnant at screening or baseline (as documented by
    a negative beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity
    of 25 IU/L or equivalent units of B-hCG). A separate baseline assessment is required
    if a negative screening pregnancy test was obtained more than 72 hours before the
    first dose of study drug. All females will be considered to be of childbearing
    potential unless they are postmenopausal (at least 12 months consecutive amenorrheic,
    in the appropriate age group, and without other known or suspected cause) or have
    been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or
    bilateral oophorectomy, all with surgery at least 1 month before dosing). Females of
    childbearing potential must not have had unprotected sexual intercourse within 30
    days prior to study entry and must agree to use a highly effective method of
    contraception, from the last menstrual period prior to initiation of treatment,
    during Treatment Cycles, and for 30 days after the final dose of study treatment, and
    have a male partner who uses a condom. Highly effective contraception includes:

    - Double barrier methods of contraception such as condom plus diaphragm or
    cervical/vault cap with spermicide

    - Placement of an intrauterine device

    - Established hormonal contraceptive methods: oral, injectable, or implant.
    Females who are using hormonal contraceptives must have been on a stable dose of
    the same hormonal contraceptive product for at least 4 weeks prior to dosing and
    must continue to use the same contraceptive during the study and for 30 days
    after study drug discontinuation. Female participants exempt from this
    requirement are participants who practice total abstinence or have a male
    partner who is vasectomized with confirmed azoospermia. If currently abstinent,
    the participant must agree to use a double barrier method as described above if
    they become sexually active during the Treatment Cycles, and for 30 days after
    study drug discontinuation

    20. Male participants must have had a successful vasectomy (confirmed azoospermia) or
    they and their female partners must meet the criteria above (ie, not of childbearing
    potential or practicing highly effective contraception and use a condom throughout
    the study period and for 30 days after study drug discontinuation)

    Exclusion Criteria:

    1. Other malignancy active within the previous 2 years except for basal or squamous cell
    skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast
    that has completed curative therapy

    2. Participants with any active autoimmune disease or a documented history of autoimmune
    disease, or history of syndrome that required systemic steroids or immunosuppressive
    medications, except for participants with vitiligo or resolved childhood
    asthma/atopy. Participants with poorly controlled asthma who require intermittent use
    of bronchodilators (such as albuterol) will be excluded from this study.

    3. Participants with inflammatory bowel disease

    4. Known human immunodeficiency virus (HIV) infection

    5. Active infection requiring therapy, including known positive tests for Hepatitis B
    surface antigen and hepatitis C virus (HCV) RNA

    6. Major surgery within 4 weeks before the first dose of study drug

    7. Concurrent medical condition requiring the use of immunosuppressive medications, or
    immunosuppressive doses of systemic or absorbable topical corticosteroids except
    inhaled or intranasal corticosteroids (with minimal systemic absorption)

    8. Inability to take oral medication, or malabsorption syndrome or any other
    uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that
    might impair the bioavailability of E7046

    9. Any other major illness that, in the investigator's judgment, will substantially
    increase the risk associated with the participant's participation in this study

    10. Use of other investigational drugs within 28 days or at least 5 half-lives (whichever
    is shorter) before study drug administration

    11. Prior exposure to drugs that are antagonists of colony stimulating factor-1 receptor
    (CSF1R)

    12. Use of any live vaccines (eg, intranasal influenza, measles, mumps, rubella, oral
    polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) within 28 days

    13. Prolongation of corrected QT [QTcF (Fridericia's corrected QT interval)] interval to
    greater than 480 msec when electrolytes balance is normal

    14. Significant cardiovascular impairment: history of congestive heart failure greater
    than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension,
    unstable angina, myocardial infarction, or stroke within 6 months of the first dose
    of study drug; or cardiac arrhythmia requiring medical treatment (including oral
    anticoagulation)

    15. Females who are pregnant (positive urine test) or breastfeeding

    16. Any history of a medical condition or a concomitant medical condition that, in the
    opinion of the investigator, would compromise the participant's ability to safely
    complete the study

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 99 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Safety/Tolerability profile of E7046 by measuring Treatment-emergent adverse event (TEAEs) and serious adverse event (SAEs)

    Maximum tolerated dose (MTD)

    Recommended Phase 2 dose (RP2D)

    Secondary Outcome Measures

    Objective Response Rate (ORR)

    Progression-free survival

    Duration of Response (DOR)

    Disease control rate

    Clinical benefit rate

    Maximum concentration (Cmax)

    Time to maximum concentration (Tmax)

    Area under the curve (AUC)

    Half life (t1/2)

    Trial Keywords

    E7046

    Advanced malignancies

    malignancies