Clinical trial NCT01271504: E7050 in Combination With Sorafenib Versus Sorafenib Alone as First Line Therapy in Participants With Hepatocellular Carcinoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Cancer
liver
hepatocellular carcinoma
phase I
phase II
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: PharmaBio Development Inc.
First posted: 2011-01-06
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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 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.

Primary outcomes:
measure: Phase 1b: Number of Participants Who Experienced Any Dose Limiting Toxicity (DLT)
timeFrame: Cycle 1 (Cycle length is 28 days)
measure: Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day -7
timeFrame: Day -7: 0-72 hours post-dose
measure: Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1
timeFrame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
measure: Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1
timeFrame: Cycle 1 Day 28: 0-24 hours post-dose
measure: Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day -7
timeFrame: Day -7: 0-72 hours post-dose
measure: Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1
timeFrame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
measure: Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1
timeFrame: Cycle 1 Day 28: 0-24 hours post-dose
measure: 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
timeFrame: Day -7: 0-72 hours post-dose
measure: 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
timeFrame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
measure: 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
timeFrame: Cycle 1 Day 28: 0-24 hours post-dose (Cycle length is 28 days)
measure: Phase 1b: t1/2: Terminal Elimination Half-life for Golvatinib When Administered in Combination With Sorafenib at Day -7
timeFrame: Day -7: 0-72 hours post-dose
measure: Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
measure: Phase 2: Number of Participants With AEs by Severity Grades
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
measure: Phase 2: Number of Participants With Adverse Events Related to Vital Signs
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
measure: Phase 2: Number of Participants With Clinically Significant Change From Baseline in Blood Pressure Including Systolic and Diastolic Blood Pressures
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
measure: Phase 2: Number of Participants With Worst Shifts Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
measure: Phase 2: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)
measure: Phase 2: Number of Participants With Markedly Abnormal Change From Baseline in Electrocardiograms (ECGs) Parameters
timeFrame: 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:
measure: Phase 2: Time to Progression (TTP)
timeFrame: From the date of randomization until the date of PD (up to approximately 3 years 11 months)
measure: Phase 2: Progression Free Survival (PFS)
timeFrame: 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)
measure: Phase 2: Percentage of Participants With PFS at Week 12
timeFrame: At 12 weeks
measure: Phase 2: Overall Survival (OS)
timeFrame: From the date of randomization until the date of death (Up to approximately 3 years 11 months)
measure: Phase 2: Percentage of Participants With Overall Response
timeFrame: From the date of randomization until disease progression or death (Up to approximately 3 years 11 months)
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: Fort Myers
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: Chapel Hill
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Nashville
country: United States
state: Tennessee
city: Brussels
country: Belgium
city: Bruxelles
country: Belgium
city: Leuven
country: Belgium
city: Rozzano
country: Italy
state: Milano
city: Modena
country: Italy
city: Pavia
country: Italy
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Lviv
country: Ukraine
city: London
country: United Kingdom
state: Greater London
city: Manchester
country: United Kingdom
state: Greater Manchester
city: Glasgow
country: United Kingdom
state: Strathclyde
Study officials:
affiliation: Quintiles, Inc.
name: Melissa J Versola, RN
role: STUDY_DIRECTOR
References: