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Advanced NeoplasmsPhase 1NCT03264664

Study of E7386 in Participants With Selected Advanced Neoplasms

A Phase 1 study testing E7386 in people with Advanced Neoplasms, run by Eisai Inc. at 10 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This study will be conducted to assess the safety/tolerability profile of E7386 as a single agent administered orally in participants with selected advanced or recurrent neoplasms and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of E7386. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Neoplasms
What is being tested?
E7386
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
10 sitesin 2 countries
Study dates
27 Jul 2017to 31 Mar 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age greater than or equal to (>=) 18 years
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Life expectancy >=12 weeks
  • Participant must have any of the following tumor types, confirmed by available histology or cytology records or current biopsy, that is advanced, nonresectable, recurrent since last antitumor therapy, in need of systemic treatment, and for which no alternative standard therapy exists:
  • Dose Escalation Part: Desmoid tumors, anaplastic thyroid cancer (ATC), endometrial cancer, melanoma, colorectal carcinoma (CRC), hepatocellular carcinoma (HCC), pancreatic cancer, prostate cancer, ovarian cancer, and head and neck cancer. Enrollment of additional tumor types will be discussed with the Sponsor and agreed on a case by case basis
  • Dose Expansion Part: HCC with CTNNB1 mutations as detected either in tumor tissue or circulating tumor DNA (ctDNA) by Sponsor-approved assay.
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  • HCC participants must have:
  • Confirmed diagnosis of HCC ii. Barcelona Clinical Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not amenable to local therapy.
  • Participants must have accessible tumors to take biopsies from a pre-designated non target lesion for performance of correlative tissue studies. If the participant has only 1 measurable lesion and no other accessible lesion, the participant can be enrolled without a biopsy upon approval by the Sponsor
  • Measurable disease meeting the following criteria:
  • At least 1 lesion of >=1.0 centimeter (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 RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI)
  • Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
  • Adequate renal function defined as serum creatinine less than or equal to (<=) 1.5*upper limit of normal (ULN), or for participants with serum creatinine greater than (>) 1.5*ULN, the calculated creatinine clearance >=30 milliliter per minute (mL/min) per the Cockcroft Gault formula (creatinine clearance >=40 mL/min for participants with HCC) is acceptable
  • Adequate bone marrow function:
  • Absolute neutrophil count (ANC) >=1500/millimeters cubed (mm^3) (>=1.5*10^3/microliters [µl])
  • Platelets >=100,000/mm^3 (>=100*10^9/Liters [L]) (platelets >=75*10^9/L for participants with HCC)
  • Hemoglobin >=9.0 grams per deciliter (g/dL)
  • Adequate liver function:
  • Total bilirubin <=1.5*ULN (<=2.0*ULN for participants with HCC)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3*ULN (<=5*ULN if participant has liver metastases or participant with HCC)
  • Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) <=1.5 (in the absence of therapeutic anticoagulation) (<=2.3 for participants with HCC)
  • Normal serum calcium and potassium levels as per local laboratory reference ranges
  • Serum magnesium greater than or equal to lower limit of normal as per local laboratory reference ranges
  • Participants must agree to take vitamin D supplements continuously as per local institutional guidelines when 25-hydroxyvitamin D levels are less than 30 nanograms per milliliter (ng/mL)
  • Willing and able to comply with all aspects of the protocol
  • Provide written informed consent prior to any study-specific screening procedures
  • Participants must have recovered from any previous anticancer therapy-related adverse events (AEs) to common terminology criteria for adverse events (CTCAE) v4.03 Grade equal to or less than (≤)1 (except for alopecia, ototoxicity, and Grade ≤2 peripheral neuropathy)

Who cannot join

  • 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
  • Prior chemotherapy, immunotherapy (tumor vaccine, cytokine or growth factor given to control the cancer), or other anti-cancer therapy within less than 4 weeks before study drug administration; prior treatment with E7386
  • Participants taking drugs, supplements, or foods that are known potent CYP3A4 inducers/inhibitors or sensitive substrates within less than 4 weeks before study drug administration
  • Prior definitive radiation therapy within less than 4 weeks and prior palliative radiotherapy within less than 2 weeks before study drug administration. Radiopharmaceuticals (strontium, samarium) within less than 8 weeks before study drug administration
  • Participants with brain or subdural metastases are not eligible, unless the metastases are asymptomatic and do not require treatment or have been adequately treated by local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks prior to study entry. Confirmation of radiographic stability must be done by comparing the brain scan (CT or MRI) performed during the Screening Period to a brain scan performed at least 4 weeks earlier (and following local therapy where applicable) using the same imaging modality as during the Screening Period. It is not the intention of this protocol to treat participants with active brain metastasis
  • Known human immunodeficiency virus (HIV) infection
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  • (Dose escalation only) Active infection requiring therapy, including known positive tests for Hepatitis B surface antigen and hepatitis C virus (HCV) ribonucleic acid (RNA) (Dose expansion only) for participants with HCC: Has dual active HBV infection (HBV) and hepatitis C virus (HCV) infection at study entry.
  • Major surgery within 4 weeks before the first dose of study drug or minor surgery within 1 week (participants must also have recovered from any surgery-related toxicities to CTCAE v4.03 Grade ≤1)
  • Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses >10 milligrams [mg]/day prednisone or equivalent) within 2 weeks before study drug administration
  • 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)
  • 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
  • Prior receipt of bisphosphonate therapy for osteoporosis or symptomatic hypercalcemia or denosumab for osteoporosis
  • Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck, or lumbar spine (L1-L4) as determined by dual energy x-ray absorptiometry (DXA) scan
  • History of symptomatic vertebral fragility fracture or any fragility fracture of the hip, pelvis, wrist, or other location (defined as any fracture without a history of trauma or because of a fall from standing height or less)
  • Moderate (25% or 40% decrease in the height of any vertebrae) or severe (>40% decrease in the height of any vertebra) morphometric vertebral fractures at baseline
  • Bone metastases and one of the following:
  • Prior history of a recent (within 1 year prior to study entry) pathologic fracture
  • Lytic lesion requiring orthopedic intervention
  • Bone lesion requiring an impending orthopedic intervention
  • Lack of treatment with a bisphosphonate or denosumab (participants may be included if such treatment is started at least 14 days prior to Cycle 1 Day 1). Participants with previous solitary bone lesions controlled with radiotherapy are eligible
  • Participants with known intolerance to study drug (or any of its excipients)
  • Participants with a fasting serum β-C-terminal telopeptide (β-CTX) concentration of >1000 picograms (pg)/mL
  • Participants with metabolic bone disease, such as hyperparathyroidism, Paget's disease, or osteomalacia
  • Participants with a recent (within 6 months) history of or a newly diagnosed insufficiency fracture
  • Use of other investigational drugs within 28 days or at least 5 half-lives (whichever is longer) before study drug administration.
  • Use of any live vaccines (example, intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guérin (BCG), yellow fever, varicella, and TY21a typhoid vaccines) within 28 days prior to the first dose of study drug
  • A prolonged QT/QT corrected (QTc) interval (QTc >450 milliseconds [ms]) as demonstrated by a repeated electrocardiogram (ECG). A history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolonged the QT/QTc interval
  • 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, left ventricular ejection fraction (LVEF) <50% , cardiac arrhythmia requiring medical treatment (including oral anticoagulation) within 6 months prior to the first dose of study drug
  • Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [β-hCG] test with a minimum sensitivity of 25 International Units per Liter [IU/L] or equivalent units of β-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
  • Females of childbearing potential who:
  • Had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (example, true abstinence if it is their preferred and usual lifestyle [defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments], an intrauterine device, a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 4 weeks after study drug discontinuation
  • Are not currently abstinent, or do not agree to refrain from sexual activity during the study period and for 4 weeks after study drug discontinuation
  • Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and who do not agree to use the same contraceptive during the study and for 4 weeks after study drug discontinuation (NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal [amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause] or have been sterilized surgically [that is, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing])
  • Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (that is, not of childbearing potential or practicing highly effective contraception throughout the study period and for 4 weeks after study drug discontinuation). No sperm donation is allowed during the study period and for 4 weeks after study drug discontinuation
  • Any other major illness, any history of a medical condition or a concomitant medical condition that, in the investigator's judgment, will substantially increase the risk associated with, or compromise the participant's participation in this study
  • For participants with HCC, participants are excluded if:
  • have a Child Pugh status of B and C.
  • clear invasion to the bile duct or portal vein invasion of Vp4.
  • symptomatic gastric or esophageal varices per Investigator's clinical judgement.
  • history of hepatic encephalopathy within 6 months prior to starting study drug.
  • (Dose Expansion only) cannot be evaluated by either triphasic liver CT or triphasic liver MRI because of allergy or other contraindication to both CT and MRI contrast agents.

Trial locations and contacts

10 sites in 2 countries.

10 sites in 2 countries

United States6 sites

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Mayo Clinic Comprehensive Cancer

    Jacksonville, Florida, 32224

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • California Liver Research Institute

    Pasadena, California, 91105

  • Mayo Clinic Comprehensive Caner

    Phoenix, Arizona, 85054

  • Mayo Clinic Comprehensive Caner

    Rochester, Minnesota, 55905

Other trials in United States

United Kingdom4 sites

  • The Beatson West of Scotland Cancer Centre

    Glasgow, Lanarkshire, G12 0YN

  • Imperial College Healthcare NHS Trust

    London, W2 1NY

  • The Christie NHS Foundation Trust

    Manchester, Lancashire, M20 4BX

  • Royal Marsden Hospital NHS Foundation Trust

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

About this study

Official title: An Open-Label, Multicenter, Phase 1 Study of E7386 in Subjects With Selected Advanced Neoplasms

This study will be conducted to assess the safety/tolerability profile of E7386 as a single agent administered orally in participants with selected advanced or recurrent neoplasms and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of E7386.

Being tested
E7386
Keywords
E7386, dose escalation, advanced or recurrent neoplasms, Hepatocellular carcinoma, HCC, CTNNB1 mutation
Medical subject headings
Neoplasms, Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • E7386Drug

    Oral immediate release tablets.

Study groups in NCT03264664
Study groupRoleWhat they receive
E7386 BIDExperimentalE7386 will be administered as a single agent orally, initially twice daily (BID) continuously in 28 days treatment cycle. The dose will be escalated in cohorts of participants subject to safety data and the absence of DLTs. Based on the emerging data after completion of Dose Escalation Part, identifying MTD or RP2D, or after a decision is made to evaluate more than one potential RP2D level, a Dose Expansion Part will be initiated. Participants will continue to receive study treatment in extension phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the study program.
Receives: Drug: E7386

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Dose-limiting Toxicities (DLTs)

    DLTs are any of the pre-specified drug-related toxicities (any toxicities considered related to E7386) occurring during Cycle 1 as assessed by the investigator. DLTs will be assessed to determine the maximum tolerated dose.

    Measured: Cycle 1 (28 days)

  2. Recommended Phase 2 Dose (RP2D)

    RP2D will be selected based on an integrated evaluation of safety, tolerability, efficacy, pharmacokinetic (PK) data, and any available pharmacodynamic (PD) data for all dose levels or all available data according to pre-specified guidelines.

    Measured: Cycle 1 (28 days)

  3. Number of Participants with Treatment Emergent Adverse Events (TEAEs)

    Measured: From the date of first dose of study drug up to 28 days after administration of study drug (up to approximately 6 years and 10 months)

Secondary outcomes (11)

  1. Objective Response Rate (ORR)

    ORR is defined as the proportion of participants achieving a best overall response of confirmed partial responses (PR) or complete response (CR), per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to less than (<) 10 millimeters (mm). PR is defined as at least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: Up to approximately 6 years and 10 months

  2. Progression-free Survival (PFS)

    PFS is defined as the time from the date of the first dose to the date of the first documentation of confirmed disease progression or death, whichever occurs first. Disease progression, per RECIST 1.1, is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

    Measured: Up to approximately 6 years and 10 months

  3. Maximum Drug Concentration (Cmax) of E7386

    Cmax is the maximum plasma concentration of a drug after administration.

    Measured: Cycle 1 Days 1 and 8: 0-12 hours postdose (Dose Escalation); Cycle 1-4 Day 1: 0-1 hours postdose (Dose Expansion) (each Cycle = 28 Days)

  4. Time to Reach the Maximum Concentration Following Drug Administration (tmax) of E7386

    tmax is the time to reach maximum concentration following drug administration.

    Measured: Cycle 1 Days 1 and 8: 0-12 hours postdose (Dose Escalation); Cycle 1-4 Day 1: 0-1 hours postdose (Dose Expansion) (each Cycle = 28 Days)

  5. Area Under the Concentration Versus Time Curve (AUC) of E7386

    AUC is a measure of actual body exposure to drug after administration of the drug.

    Measured: Cycle 1 Days 1 and 8: 0-12 hours postdose (Dose Escalation); Cycle 1-4 Day 1: 0-1 hours postdose (Dose Expansion) (each Cycle = 28 Days)

  6. Elimination Half-life (t1/2) of E7386

    t1/2 is the time required for the concentration of the drug to reach half of its original value.

    Measured: Cycle 1 Days 1 and 8: 0-12 hours postdose (Dose Escalation); Cycle 1-4 Day 1: 0-1 hours postdose (Dose Expansion) (each Cycle = 28 Days)

  7. Apparent Total Body Clearance (CL/F) of E7386

    CL/F is the volume of plasma cleared of drug per unit time.

    Measured: Cycle 1 Days 1 and 8: 0-12 hours postdose (Dose Escalation); Cycle 1-4 Day 1: 0-1 hours postdose (Dose Expansion) (each Cycle = 28 Days)

  8. Volume of Distribution (Vd) of E7386

    Vd is the apparent volume in which a drug is distributed.

    Measured: Cycle 1 Days 1 and 8: 0-12 hours postdose (Dose Escalation); Cycle 1-4 Day 1: 0-1 hours postdose (Dose Expansion) (each Cycle = 28 Days)

  9. Renal Clearance (CLr) of E7386

    Measured: Cycle 1 Days 1 and 8: 0-24 hours postdose (Dose Escalation) (each Cycle = 28 Days)

  10. Accumulation Ratio (R) of E7386

    R indicates the extent to which drug accumulates.

    Measured: Cycle 1 Days 1 and 8: 0-12 hours postdose (Dose Escalation); Cycle 1-4 Day 1: 0-1 hours postdose (Dose Expansion) (each Cycle = 28 Days)

  11. Fraction Excreted (fe) of E7386

    Measured: Cycle 1 Days 1 and 8: 0-24 hours postdose (Dose Escalation) (each Cycle = 28 Days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Aug 2017
  2. Study start27 Jul 2017
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion31 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03264664
Sponsor's protocol ID
E7386-G000-101
Other IDs
2016-004881-25, 2016
Status last verified
Jun 2026
First submitted
25 Aug 2017
Last updated
8 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Evans TRJ, Cook N, El-Khoueiry A, Pinato DJ, Tran NH, Hsiehchen D, Mena E, Meyer T, Wu J, Pathak SM, Paoletti C, Dutta L, Okpara CE, Lopez JS. A first-in-human, open-label multicentre Phase 1 study of the orally administered E7386 in patients with selected advanced neoplasms. Br J Cancer. 2026 Jun 4. doi: 10.1038/s41416-026-03488-w. Online ahead of print.

    PubMed 42243349

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing E7386 in people with Advanced Neoplasms, run by Eisai Inc. at 10 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: Cycle 1 (28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03264664, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2026.

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