E7050 in Combination With Sorafenib Versus Sorafenib Alone as First Line Therapy in Participants With Hepatocellular Carcinoma

April 16, 2021 updated by: Eisai Inc.

An Open-Label, Multicenter, Randomized, Phase Ib/II Study of E7050 in Combination With Sorafenib Versus Sorafenib Alone as First Line Therapy in Patients With Hepatocellular Carcinoma

The purpose of this study is to determine whether patients with hepatocellular carcinoma who receive either E7050 administered with Sorafenib or Sorafenib alone experience greater benefit (cancer responds to treatment) when E7050 is administered with Sorafenib.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This open-label, multicenter, randomized study will consist of a Phase Ib: a safety run-in period with 3 ascending doses of E7050 in combination with sorafenib; and a Phase II portion: a randomized 2-arm period. Approximately 95 patients with hepatocellular carcinoma will be enrolled in the study (10-15 patients in the Phase Ib portion and 80 patients in the Phase II portion). Patients will only participate in either the Phase Ib or the Phase II portion of the study. In both Phase Ib and phase II, Patients will receive study treatment (E7050 plus sorafenib or sorafenib alone) until the occurrence of progressive disease (PD)for approximately six 28-day cycles (24 weeks). After 6 cycles. ath the discretion of the Investigator and in consultation with the Medical Monitor, patients who are experiencing clinical benefit may continue E7050, with or without sorafenib (Arm 1), or may continue sorafenib alone (Arm 2), depending on the original randomization treatment arm, for as long as clinical benefit is sustained and the treatment is well tolerated. Patients will be followed until death following completion of therapy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
102

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1070
      • Bruxelles, Belgium, 1200
      • Leuven, Belgium, 3000
  • Italy
      • Modena, Italy, 40124
      • Pavia, Italy, 27100
    • Milano
      • Rozzano, Milano, Italy, 20089
  • Spain
      • Madrid, Spain, 28046
      • Madrid, Spain, 28034
      • Madrid, Spain, 28007
      • Madrid, Spain, 28050
  • Ukraine
      • Dnipropetrovsk, Ukraine, 49102
      • Donetsk, Ukraine, 83092
      • Kharkiv, Ukraine, 61037
      • Lviv, Ukraine, 79031
  • United Kingdom
    • Greater London
      • London, Greater London, United Kingdom, WC1E 6BT
    • Greater Manchester
      • Manchester, Greater Manchester, United Kingdom, M20 4BX
    • Strathclyde
      • Glasgow, Strathclyde, United Kingdom, G12 OYN
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85715
    • Florida
      • Fort Myers, Florida, United States, 33905
      • Saint Petersburg, Florida, United States, 33705
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
    • Ohio
      • Cincinnati, Ohio, United States, 45267
      • Toledo, Ohio, United States, 43623
    • Tennessee
      • Nashville, Tennessee, United States, 37203

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  • Unresectable locally advanced or metastatic HCC;
  • Histologic confirmation not required if other diagnostic criteria are met;
  • No previous systemic anti-cancer therapy permitted (2 prior systemic anti-cancer regimen are allowed in Phase Ib). Previous chemoembolization, radioembolization, radiofrequency ablation, or other local ablative therapies are permitted if greater than 6 weeks of first day of study-defined treatment;
  • ECOG PS 0 or 1; Child-Pugh Cirrhotic Status A or B with a score of 7;
  • Blood pressure must be well-controlled (less than or equal to 140/90 mmHg at screening) with or without antihypertensive medication. Patients must have no history of hypertensive crisis or hypertensive encephalopathy;

Exclusion Criteria

  • Previously received E7050 anti-cmet, or anti-angiogenic therapy (prior anti-angiogenic therapy is permitted in Phase Ib only);
  • Presence of brain metastases, unless the patient has received adequate treatment at least 4 weeks prior to randomization, and is stable, asymptomatic, and off steroids for at least 4 weeks prior to randomization;
  • Palliative radiotherapy is not permitted throughout the study period;
  • Active hemoptysis
  • Serious non-healing wound, ulcer, or active bone fracture;
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to commencing study treatment, or anticipation of need for a major surgical procedure during the course of the study;
  • Clinically significant gastrointestinal bleeding (bleeding requiring procedural intervention, eg. variceal banding, transjugular intrahepatic portosystemic shunt (TIPS) procedure, arterial embolization, topical coagulation therapy) within 6 months prior to first dose.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Phase Ib: Cohort 1,2, and 3
Phase Ib: Cohort 1; 200 mg E7050 + 400 mg Sorafenib Cohort 2; 300 mg E7050 + 400 mg Sorafenib Cohort 3; 400 mg E7050 + Sorafenib
Drug: Sorafenib
Phase Ib: Cohort 1; 200 mg E7050 + 400 mg Sorafenib Cohort 2; 300 mg E7050 + 400 mg Sorafenib Cohort 3; 400 mg E7050 + Sorafenib
Drug: Sorafenib

E7050 given orally at 200, 300 or 400 mg once daily.

Sorafenib given orally, 400 mg twice daily.
Active Comparator: Phase II: Arm 1; E7050 + Sorafenib
Phase II: Arm 1; E7050 + 400 mg Sorafenib Arm 2; 400 mg Sorafenib
Drug: Sorafenib
Phase Ib: Cohort 1; 200 mg E7050 + 400 mg Sorafenib Cohort 2; 300 mg E7050 + 400 mg Sorafenib Cohort 3; 400 mg E7050 + Sorafenib
Drug: Sorafenib

E7050 given orally at 200, 300 or 400 mg once daily.

Sorafenib given orally, 400 mg twice daily.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Phase 1b: Number of Participants Who Experienced Any Dose Limiting Toxicity (DLT)
Time Frame: Cycle 1 (Cycle length is 28 days)
DLTs were defined as clinically significant adverse events (AEs) (non-hematological, hematological and other events) occurring less than or equal to (<=) 28 days after commencing study treatment and considered to be at least possibly or probably related to study drug by the Investigator. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v.4.0).
Cycle 1 (Cycle length is 28 days)
Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day -7
Time Frame: Day -7: 0-72 hours post-dose
Day -7: 0-72 hours post-dose
Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1
Time Frame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1
Time Frame: Cycle 1 Day 28: 0-24 hours post-dose
Cycle 1 Day 28: 0-24 hours post-dose
Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day -7
Time Frame: Day -7: 0-72 hours post-dose
Day -7: 0-72 hours post-dose
Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1
Time Frame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1
Time Frame: Cycle 1 Day 28: 0-24 hours post-dose
Cycle 1 Day 28: 0-24 hours post-dose
Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day -7
Time Frame: Day -7: 0-72 hours post-dose
Day -7: 0-72 hours post-dose
Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1
Time Frame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1
Time Frame: Cycle 1 Day 28: 0-24 hours post-dose (Cycle length is 28 days)
Cycle 1 Day 28: 0-24 hours post-dose (Cycle length is 28 days)
Phase 1b: t1/2: Terminal Elimination Half-life for Golvatinib When Administered in Combination With Sorafenib at Day -7
Time Frame: Day -7: 0-72 hours post-dose
Day -7: 0-72 hours post-dose
Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Phase 2: Number of Participants With AEs by Severity Grades
Time Frame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
AE severity was graded using CTCAE version 4.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death related to the AE. All AEs graded as 4 or 5 were considered to be serious. Higher grade indicates more severe condition.
From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Phase 2: Number of Participants With Adverse Events Related to Vital Signs
Time Frame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Number of participants are reported with AEs related to Vital signs including body temperature, respiratory rate, heart rate, height, and weight.
From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Phase 2: Number of Participants With Clinically Significant Change From Baseline in Blood Pressure Including Systolic and Diastolic Blood Pressures
Time Frame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Phase 2: Number of Participants With Worst Shifts Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
Time Frame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Number of participants with worst shifts post baseline in ECOG-PS levels were reported. ECOG has 6 levels (0-5). Level 0 is the best status (fully active, able to carry on all pre-disease performance without restriction); Level 1 is mildly restricted (Restricted in physically strenuous activity but ambulatory ad able to carry out work of a light or sedentary nature, e.g. light house work, office work); Level 2 is more restricted (Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours); Level 3 is restricted (Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours); Level 4 is highly restricted (completely disabled; cannot carry on any selfcare; totally confined to bed or chair); and Level 5 is death (dead).
From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Phase 2: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
Time Frame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
Phase 2: Number of Participants With Markedly Abnormal Change From Baseline in Electrocardiograms (ECGs) Parameters
Time Frame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase 2: Time to Progression (TTP)
Time Frame: From the date of randomization until the date of PD (up to approximately 3 years 11 months)
TTP was defined as the time from the date of randomization until the date of PD of such participants disease based on independent assessments according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. PD was defined as at least a 20% increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. TTP was estimated and analyzed using Kaplan-Meier (K-M) method.
From the date of randomization until the date of PD (up to approximately 3 years 11 months)
Phase 2: Progression Free Survival (PFS)
Time Frame: From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 3 years 11 months)
PFS was defined as the time from the date of randomization of a participant until (1) the date of first documented progression (2) the date of such participant's death due to any cause based on independent assessments according to RECIST v. 1.1. PD was defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using KM method.
From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 3 years 11 months)
Phase 2: Percentage of Participants With PFS at Week 12
Time Frame: At 12 weeks
The PFS rate at week 12 was defined as the percentage of participants who were still alive without disease progression at 12 weeks from the date of randomization. PFS was defined as the time from the date of randomization of a participant until (1) the date of first documented progression (2) the date of such participant's death due to any cause based on independent assessments according to RECIST v. 1.1. PD was defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.
At 12 weeks
Phase 2: Overall Survival (OS)
Time Frame: From the date of randomization until the date of death (Up to approximately 3 years 11 months)
OS was defined as the time from the date of randomization until the date of death. Participants were censored at the date of last known alive. OS was analyzed using K-M method.
From the date of randomization until the date of death (Up to approximately 3 years 11 months)
Phase 2: Percentage of Participants With Overall Response
Time Frame: From the date of randomization until disease progression or death (Up to approximately 3 years 11 months)
Overall response rate was defined as percentage of participants with best confirmed response (CR) or partial response (PR) assessed by investigator per RECIST v1.1. A confirmatory scan was required after no less than 4 weeks and no later than 8 weeks, starting on the date that the response was first recorded. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<)10 mm. PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
From the date of randomization until disease progression or death (Up to approximately 3 years 11 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eisai Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
PharmaBio Development Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Melissa J Versola, RN, Quintiles, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 19, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 23, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 23, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 5, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 5, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 6, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 12, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 16, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • E7050-701
  • 2011-000752-41 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings