Study of E7386 in Participants With Selected Advanced Neoplasms

NCT03264664 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: E7386-G000-1012016-004881-25
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 10

Brief 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.

Conditions

Advanced Neoplasms

Keywords

E7386; dose escalation; advanced or recurrent neoplasms; Hepatocellular carcinoma; HCC; CTNNB1 mutation

Outcome Measures

Primary Outcomes (3)

• 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.

  Cycle 1 (28 days)

• 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.

  Cycle 1 (28 days)

• Number of Participants with Treatment Emergent Adverse Events (TEAEs)

  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)

• Objective Response Rate (ORR)

  Up to approximately 6 years and 10 months

• Progression-free Survival (PFS)

  Up to approximately 6 years and 10 months

• Maximum Drug Concentration (Cmax) of E7386

  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)

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

  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)

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

  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)

Study Arms (1)

E7386 BID

EXPERIMENTAL

E7386 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.

Drug: E7386

Interventions

E7386 DRUG

Oral immediate release tablets.

E7386 BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 \[µl\])

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

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (10)

Mayo Clinic Comprehensive Caner

Phoenix, Arizona, 85054, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Mayo Clinic Comprehensive Cancer

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic Comprehensive Caner

Rochester, Minnesota, 55905, United States

Location

The Beatson West of Scotland Cancer Centre

Glasgow, Lanarkshire, G12 0YN, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, Lancashire, M20 4BX, United Kingdom

Location

Royal Marsden Hospital NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Royal Free London NHS Foundation Trust, Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W2 1NY, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Carcinoma, Hepatocellular

Interventions

E-7386

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2017
• First Posted: August 29, 2017
• Study Start: July 27, 2017
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 6, 2026

Record last verified: 2025-06

Locations

US (5); GB (5)