Clinical trial NCT02834780: Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Participants With Advanced Hepatocellular Carcinoma
Official title: An Open-Label Multicenter Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Subjects With Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Hepatocellular Carcinoma
Hepatocellular Carcinoma
Liver Cancer
Liver Neoplasms
Hepatic Cancer
Hepatic Carcinoma
Keywords: Advanced Hepatocellular Carcinoma
H3B-6527
Fibroblast growth factor receptor 4 (FGFR4)
Fibroblast growth factor 19 (FGF19)
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Eisai Inc.
First posted: 2016-07-15
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of H3B-6527, and to assess the safety, tolerability and pharmacokinetics of H3B-6527.


Eligibility criteria: Inclusion criteria:

1. Participants with hepatocellular carcinoma.
2. Must have had at least one prior standard-of-care therapy, unless contraindicated.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
4. Must be willing to undergo a biopsy up to 8 weeks before administration of H3B-6527 on Cycle 1 Day 1 for part 2 (dose expansion).
5. Adequate bone marrow and organ function.

Exclusion criteria:

1. Uncontrolled significant active infections, except hepatitis B virus (HBV) or hepatitis C virus (HCV).
2. Known human immunodeficiency virus infection.
3. Presence of gastric or esophageal varices requiring active treatment.
4. Previous treatment with a selective FGF19-FGFR4 targeted therapy.
5. Females of childbearing potential, or males who have not had a successful vasectomy, who are unable or unwilling to follow adequate contraceptive measures.
6. Hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption.

Primary outcomes:
measure: Part 1, Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs) Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
timeFrame: Cycle 1 (Cycle length = 21 days)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose of study drug up to approximately 36.7 months
measure: Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
timeFrame: From baseline up to approximately 36.7 months
measure: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters
timeFrame: From baseline up to approximately 36.7 months
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters
timeFrame: From baseline up to approximately 36.7 months
Secondary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527
timeFrame: Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)
measure: Maximum Observed Plasma Concentration (Cmax) of H3B-6527
timeFrame: Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)
measure: Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527
timeFrame: Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)
measure: Part 2, Dose Expansion Phase: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
timeFrame: From the first dose date until disease progression/recurrence or up to approximately 36.7 months
measure: Part 2, Dose Expansion Phase: Duration of Response (DOR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
timeFrame: From the date of first documented CR or PR up to approximately 36.7 months
measure: Part 2, Dose Expansion Phase: Progression-free Survival (PFS) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
timeFrame: From the first dose date to the date of the first documentation of PD as determined by the investigator or death (whichever occurs first) up to approximately 36.7 months
measure: Part 2, Dose Expansion Phase: Overall Survival (OS)
timeFrame: From the date of first dose of study drug until date of death from any cause (up to approximately 36.7 months)
measure: Part 2, Dose Expansion Phase: Time to Response (TTR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
timeFrame: From date of first dose of study drug until CR or PR (up to approximately 36.7 months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center
state: California
city: Washington
country: United States
facility: Georgetown Unversity Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Chicago
country: United States
facility: Northwestern Unversity
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Hackensack
country: United States
facility: John theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Durham
country: United States
facility: Duke University Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylsvania - Perelman Cancer Center for Advanced Medicine
state: Pennsylvania
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Woluwe-Saint-Lambert
country: Belgium
facility: UCL Cliniques universitaires Saint-Luc
state: Brussels
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: Jurvanski Cancer Center
state: Ontario
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lille
country: France
facility: Centre Oscar Lambret
city: Pessac
country: France
facility: Hôpital Haut-Lévêque - CHU de Bordeaux
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Meldola
country: Italy
facility: IRCCS Istituto Scientifico Romagnolo per lo studio e la cura dei tumori - U.O. di Oncologia Medica
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele S.r.l. - PPDS
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria - Policlinico di Modena
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Barnaul
country: Russian Federation
facility: Altay Regional Oncology Center
state: Altay, Re
city: Moscow
country: Russian Federation
facility: Russian Oncology Research Center n a N N Blokhin
city: Omsk
country: Russian Federation
facility: Omsk Regional Oncology Center
city: Saint Petersburg
country: Russian Federation
facility: Railway Clinical Hospital JSC RZhD
city: Saint Petersburg
country: Russian Federation
facility: City Clinical Oncology Dispensary
city: Singapore
country: Singapore
facility: National University Cancer Insitute
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Badajoz
country: Spain
facility: Hospital Universitario de Badajoz
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: START Madrid FJD, Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK - SCRI - PPDS
Study officials:
References: