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

Eisai Inc.10 sites in 2 countries60 target enrollmentJuly 27, 2017

ConditionsAdvanced Neoplasms

InterventionsE7386

DrugsE7386

Overview

Phase: Phase 1
Intervention: E7386
Conditions: Advanced Neoplasms
Sponsor: Eisai Inc.
Enrollment: 60
Locations: 10
Primary Endpoint: Number of Participants With Dose-limiting Toxicities (DLTs)
Status: Active, not recruiting
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

July 27, 2017

End Date

March 31, 2027

Last Updated

last month

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Eisai Inc.

Responsible Party

Sponsor

Eligibility Criteria

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 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:

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
•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)

Arms & Interventions

E7386 BID

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.

Intervention: E7386

Outcomes

Primary Outcomes

Number of Participants With Dose-limiting Toxicities (DLTs)

Time Frame: Cycle 1 (28 days)

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.

Recommended Phase 2 Dose (RP2D)

Time Frame: Cycle 1 (28 days)

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.

Number of Participants with Treatment Emergent Adverse Events (TEAEs)

Time Frame: 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

Objective Response Rate (ORR)(Up to approximately 6 years and 10 months)
Progression-free Survival (PFS)(Up to approximately 6 years and 10 months)
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))
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))
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))
Elimination Half-life (t1/2) 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))
Apparent Total Body Clearance (CL/F) 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))
Volume of Distribution (Vd) 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))
Renal Clearance (CLr) of E7386(Cycle 1 Days 1 and 8: 0-24 hours postdose (Dose Escalation) (each Cycle = 28 Days))
Fraction Excreted (fe) of E7386(Cycle 1 Days 1 and 8: 0-24 hours postdose (Dose Escalation) (each Cycle = 28 Days))
Accumulation Ratio (R) 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))