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

NCT01271504 | Completed Phase 1 Results

• 2 other identifiers: E7050-7012011-000752-41
• Study Type: interventional
• Target: 102
• Locations: 6 countries
• Sites: 24

Brief Summary

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.

Conditions

Hepatocellular Carcinoma

Keywords

Cancer; liver; hepatocellular carcinoma; phase I; phase II

Outcome Measures

Primary Outcomes (18)

• Phase 1b: Number of Participants Who Experienced Any Dose Limiting Toxicity (DLT)

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  Day -7: 0-72 hours post-dose

• Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  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

  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

  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

  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)

  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

  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

  From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)

Secondary Outcomes (5)

• Phase 2: Time to Progression (TTP)

  From the date of randomization until the date of PD (up to approximately 3 years 11 months)

• Phase 2: Progression Free Survival (PFS)

  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

  At 12 weeks

• Phase 2: Overall Survival (OS)

  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

  From the date of randomization until disease progression or death (Up to approximately 3 years 11 months)

Study Arms (2)

Phase Ib: Cohort 1,2, and 3

ACTIVE COMPARATOR

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 II: Arm 1; E7050 + Sorafenib

ACTIVE COMPARATOR

Phase II: Arm 1; E7050 + 400 mg Sorafenib Arm 2; 400 mg Sorafenib

Drug: Sorafenib

Interventions

Sorafenib DRUG

Phase Ib: Cohort 1; 200 mg E7050 + 400 mg Sorafenib Cohort 2; 300 mg E7050 + 400 mg Sorafenib Cohort 3; 400 mg E7050 + Sorafenib

Phase Ib: Cohort 1,2, and 3

Eligibility Criteria

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

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eisai Inc.: lead
• PharmaBio Development Inc.: collaborator

Study Sites (24)

Unknown Facility

Tucson, Arizona, 85715, United States

Location

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Fort Myers, Florida, 33905, United States

Location

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St. Petersburg, Florida, 33705, United States

Location

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Chapel Hill, North Carolina, 27599, United States

Location

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Cincinnati, Ohio, 45267, United States

Location

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Toledo, Ohio, 43623, United States

Location

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Nashville, Tennessee, 37203, United States

Location

Unknown Facility

Brussels, 1070, Belgium

Location

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Brussels, 1200, Belgium

Location

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Leuven, 3000, Belgium

Location

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Rozzano, Milano, 20089, Italy

Location

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Modena, 40124, Italy

Location

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Pavia, 27100, Italy

Location

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Madrid, 28007, Spain

Location

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Madrid, 28034, Spain

Location

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Madrid, 28046, Spain

Location

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Madrid, 28050, Spain

Location

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Dnipropetrovsk, 49102, Ukraine

Location

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Donetsk, 83092, Ukraine

Location

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Kharkiv, 61037, Ukraine

Location

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Lviv, 79031, Ukraine

Location

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London, Greater London, WC1E 6BT, United Kingdom

Location

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Manchester, Greater Manchester, M20 4BX, United Kingdom

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Glasgow, Strathclyde, G12 OYN, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Neoplasms

Interventions

Sorafenib

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

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Study Officials

• Melissa J Versola, RN

  Quintiles, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 5, 2011
• First Posted: January 6, 2011
• Study Start: July 19, 2011
• Primary Completion: June 23, 2015
• Study Completion: June 23, 2015
• Last Updated: May 12, 2021
• Results First Posted: April 8, 2021

Record last verified: 2017-08

Locations

BE (3); ES (4); US (7); GB (3); IT (3); UA (4)