Study of E7386 in Participants With Selected Advanced Neoplasms

Running, not enrolling · Phase 1

Conditions studied: Advanced Neoplasms

In brief

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.

Key facts

Study ID

NCT03264664

Run by

Eisai Inc.

People needed

60

Starts

2017-07-27

Expected to finish

2027-03-31

Last updated by the study team

2026-06-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• HCC participants must have:
• i. 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

You may not qualify if…

• 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
• (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.

Where it is running

• Mayo Clinic Comprehensive Caner — Phoenix, Arizona, United States
• USC Norris Comprehensive Cancer Center — Los Angeles, California, United States
• California Liver Research Institute — Pasadena, California, United States
• Mayo Clinic Comprehensive Cancer — Jacksonville, Florida, United States
• Mayo Clinic Comprehensive Caner — Rochester, Minnesota, United States
• UT Southwestern Medical Center — Dallas, Texas, United States
• The Beatson West of Scotland Cancer Centre — Glasgow, Lanarkshire, United Kingdom
• The Christie NHS Foundation Trust — Manchester, Lancashire, United Kingdom
• Royal Marsden Hospital NHS Foundation Trust — Sutton, Surrey, United Kingdom
• Imperial College Healthcare NHS Trust — London, United Kingdom

Full record on ClinicalTrials.gov

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