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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
PharmaBio Development Inc.
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01271504
First received: January 5, 2011
Last updated: June 20, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: Sorafenib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Safety Parameters-Adverse Event (AEs) [ Time Frame: Until study termination ] [ Designated as safety issue: Yes ]

    Phase Ib: To determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with sorafenib in patients with locally advanced or metastatic HCC;

    Phase II: To evaluate the safety and tolerability of E7050 when administered in combination with sorafenib as compared with sorafenib alone in patients with locally advanced or metastatic HCC.


  • Safety Parameter-Concomitant Meds [ Time Frame: Until study termination ] [ Designated as safety issue: Yes ]

    Phase Ib: To determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with sorafenib in patients with locally advanced or metastatic HCC;

    Phase II: To evaluate the safety and tolerability of E7050 when administered in combination with sorafenib as compared with sorafenib alone in patients with locally advanced or metastatic HCC.


  • Safety Parameter- Clinical Laboratory Evaluations [ Time Frame: Day 1 and every 28 days until study termination; 3 years ] [ Designated as safety issue: Yes ]

    Phase Ib: To determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with sorafenib in patients with locally advanced or metastatic HCC;

    Phase II: To evaluate the safety and tolerability of E7050 when administered in combination with sorafenib as compared with sorafenib alone in patients with locally advanced or metastatic HCC.


  • Safety Parameter-ECGS [ Time Frame: Day 1 and every 28 days until study termination; 3 years ] [ Designated as safety issue: Yes ]

    Phase Ib: To determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with sorafenib in patients with locally advanced or metastatic HCC;

    Phase II: To evaluate the safety and tolerability of E7050 when administered in combination with sorafenib as compared with sorafenib alone in patients with locally advanced or metastatic HCC.


  • Safety Parameters-Vital signs [ Time Frame: until study termination ] [ Designated as safety issue: Yes ]

    Phase Ib: To determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with sorafenib in patients with locally advanced or metastatic HCC;

    Phase II: To evaluate the safety and tolerability of E7050 when administered in combination with sorafenib as compared with sorafenib alone in patients with locally advanced or metastatic HCC.


  • Safety Parameters- ECOG PS [ Time Frame: until study termination ] [ Designated as safety issue: Yes ]

    Phase Ib: To determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with sorafenib in patients with locally advanced or metastatic HCC;

    Phase II: To evaluate the safety and tolerability of E7050 when administered in combination with sorafenib as compared with sorafenib alone in patients with locally advanced or metastatic HCC.



Secondary Outcome Measures:
  • Efficacy Parameter [ Time Frame: Time to progression (TTP)-Until the date of first documented progression of such patient's disease ] [ Designated as safety issue: No ]

    Phase Ib: To determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with sorafenib in patients with locally advanced or metastatic HCC;

    Phase II: To evaluate the safety and tolerability of E7050 when administered in combination with sorafenib as compared with sorafenib alone in patients with locally advanced or metastatic HCC.


  • Efficacy Parameter [ Time Frame: Overall survival (OS)-Until the date of first documented progresssion of such patient's disease ] [ Designated as safety issue: No ]

    Phase Ib: To determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with sorafenib in patients with locally advanced or metastatic HCC;

    Phase II: To evaluate the safety and tolerability of E7050 when administered in combination with sorafenib as compared with sorafenib alone in patients with locally advanced or metastatic HCC.


  • Efficacy Parameter [ Time Frame: Overall response rate (ORR)-Until the date of first documented progression of such patient's disease ] [ Designated as safety issue: No ]

    Phase Ib: To determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with sorafenib in patients with locally advanced or metastatic HCC;

    Phase II: To evaluate the safety and tolerability of E7050 when administered in combination with sorafenib as compared with sorafenib alone in patients with locally advanced or metastatic HCC.



Estimated Enrollment: 95
Study Start Date: April 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Active Comparator: Phase II: Arm 1; E7050 + Sorafenib
Phase II: Arm 1; E7050 + 400 mg Sorafenib Arm 2; 400 mg Sorafenib
Drug: Sorafenib

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

Sorafenib given orally, 400 mg twice daily.


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 >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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01271504

Locations
United States, Arizona
Tucson, Arizona, United States, 85715
United States, Florida
Fort Myers, Florida, United States, 33905
St. Petersburg, Florida, United States, 33705
United States, North Carolina
Chapell Hill, North Carolina, United States, 27599
United States, Ohio
Cincinnati, Ohio, United States, 45267
Toledo, Ohio, United States, 43623
United States, Tennessee
Nashville, Tennessee, United States, 37203
Belgium
Brussels, Belgium, 1070
Bruxelles, Belgium, 1200
Leuven, Belgium, 3000
Italy
Rozzano, Milano, Italy, 20089
Modena, Italy, 40124
Pavia, Italy, 27100
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
London, Greater London, United Kingdom, WC1E 6BT
Manchester, Greater Manchester, United Kingdom, M20 4BX
Glasgow, Strathclyde, United Kingdom, G12 OYN
Sponsors and Collaborators
Eisai Inc.
PharmaBio Development Inc.
Investigators
Study Director: Melissa J Versola, RN Quintiles
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01271504     History of Changes
Other Study ID Numbers: E7050-701, 2011-000752-41
Study First Received: January 5, 2011
Last Updated: June 20, 2014
Health Authority: Ukraine: Ministry of Health
United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
Cancer
liver
hepatocellular carcinoma
phase I
phase II

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014