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

  • End date
    May 31, 2024
  • participants needed
  • sponsor
    Eisai Inc.
Updated on 14 October 2022


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.

Condition Advanced Neoplasms
Treatment E7386
Clinical Study IdentifierNCT03264664
SponsorEisai Inc.
Last Modified on14 October 2022


Yes No Not Sure

Inclusion Criteria

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 specific mutations as detected either in tumor tissue or circulating tumor DNA (ctDNA) by Sponsor-approved assay
HCC participants must have
Measurable disease meeting the following criteria
Confirmed diagnosis of HCC
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)
Barcelona Clinical Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not amenable to local therapy
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
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
Adequate bone marrow function
Adequate renal function defined as serum creatinine less than or equal to (<=)
Hemoglobin >=9.0 grams per deciliter (g/dL)
5 _upper limit of normal (ULN), or for participants with serum creatinine
Adequate liver function
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
Normal serum calcium and potassium levels as per local laboratory reference ranges
Absolute neutrophil count (ANC) >=1500/millimeters cubed (mm^3) (>=1.510^3/microliters [µl])
Serum magnesium greater than or equal to lower limit of normal as per local laboratory reference ranges
Platelets >=100,000/mm^3 (>=100 _10^9/Liters [L]) (platelets >=75_10^9/L for participants with HCC)
Willing and able to comply with all aspects of the protocol
Provide written informed consent prior to any study-specific screening procedures
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)
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)
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)

Exclusion Criteria

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
Participants taking drugs, supplements, or foods that are known potent CYP3A4 inducers/inhibitors or substrates with narrow indices within less than 4 weeks before study drug administration
Prior definitive radiation therapy within less than 6 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
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)
Prior receipt of bisphosphonate therapy for osteoporosis or symptomatic hypercalcemia or denosumab for osteoporosis
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
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
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
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
(Dose escalation only) Active infection requiring therapy, including known positive tests for Hepatitis B surface antigen and hepatitis C virus (HCV) ribonucleic acid (RNA)
Lytic lesion requiring orthopedic intervention
(Dose expansion only) for participants with HCC: Has dual active HBV infection (HBV) and hepatitis C virus (HCV) infection at study entry
Bone lesion requiring an impending orthopedic intervention
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)
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 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. For drugs such as monoclonal antibodies with half-lives >10 days, at least 56 days is required
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 of childbearing potential who
Are not currently abstinent, or do not agree to refrain from sexual activity during the study period and for 28 days after study drug discontinuation
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 28 days after study drug discontinuation
Participants with known intolerance to study drug (or any of its excipients)
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 28 days 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])
Participants with a fasting serum β-C-terminal telopeptide (β-CTX) concentration of >1000 picograms (pg)/mL
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
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
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
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 28 days after study drug discontinuation). No sperm
donation is allowed during the study period and for 28 days after study drug
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
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