Clinical trial NCT02421185: Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-42756493 (Erdafitinib) in Participants With Advanced Hepatocellular Carcinoma
Official title: A Phase 1/2a Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-42756493, a Pan-Fibroblast Growth Factor Receptor (FGFR) Tyrosine Kinase Inhibitor, in Subjects With Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Hepatocellular
Keywords: Carcinoma, Hepatocellular
JNJ 42756493
a pan-Fibroblast Growth Factor Receptor Tyrosine Kinase Inhibitor
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-04-20
Enrollment: 53
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 recommended Phase 2 dose \[RP2D\]) and the objective response rate of JNJ-42756493 (erdafitinib) in advanced hepatocellular carcinoma (HCC) participants with fibroblast growth factor (FGF) 19 amplification.

Detailed description: This is an open-label (all people know the identity of the intervention), multicenter (when more than one hospital or medical school team work on a medical research study), 2 parts (First, dose escalation Phase and second, dose expansion Phase) study to evaluate the safety, pharmacokinetics, pharmacodynamics, and clinical responses of JNJ-42756493 (erdafitinib) in Asian participants with advanced HCC. The duration of study will be approximately 11 months per participant. The study consists of 2 periods: Screening (28 days before study commences on Day 1); Open-label Treatment (dose escalation portion of the trial \[Part 1\]), participants are enrolled into cohorts at increasing dose levels of JNJ-42756493 (erdafitinib) in 28 day treatment cycles. Part 2, the cohort expansion part of the trial, will further explore the recommended phase 2 dose (RP2D) of JNJ-42756493 (erdafitinib) as determined in Part 1; and follow-up Phase (up to 6 months). Blood samples will be collected for evaluation of safety, pharmacokinetics, pharmacodynamics, and predictive biomarkers at pre-dose and post-dose of study treatment. Recommended Phase 2 dose (RP2D) for JNJ-42756493 (erdafitinib) will be evaluated primarily. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed hepatocellular carcinoma (HCC). (histology or cytology from prior tumor biopsy specimen is acceptable). For Part 1 continuous dosing regimen and Part 2, HCC participants must have fibroblast growth factor (FGF) 19 amplification based on central laboratory results
* Participant must have advanced disease and meet all the following criteria: Disease progression after previous surgical or local-regional therapy, if any; Disease ineligible for surgical or local-regional therapy or systemic therapy; Received no more than 1 line of systemic therapy (Participants who are intolerant to previous systemic therapy are allowed.)
* Cirrhotic status of Child-Pugh class A: Participants with Child-Pugh class B score of 7 may be considered in Part 2 if no pharmacokinetic (PK) and safety issues are identified in Part 1 from subjects with Child-Pugh class A
* Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1
* Participants with adequate bone marrow, liver, renal function, and electrolytes according to protocol-defined criteria within the 14 days before the first dose of study drug
* Negative pregnancy test (urine or serum beta human chorionic gonadotropin \[beta (b)-hCG\]) at Screening for women of child bearing potential who are sexually active

Exclusion Criteria:

* Received systemic chemotherapy, targeted therapies, definitive radiotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and mitomycin C, within 6 weeks; in the case of immunotherapy, within 4 weeks) before the first administration of study drug
* Prior liver transplant
* Known fibrolamellar HCC or mixed cholangiocarcinoma and HCC
* Clinically active serious infections greater than (\>) Common Terminology Criteria for adverse events (AEs) grade 2
* Participants with persistent calcium or phosphate \> upper limits of normal (ULN) during screening (within 14 days prior to Day 1 of Cycle 1 up until pre-dose of Cycle 1) and despite medical management of calcium or phosphate levels

Primary outcomes:
measure: Part 1:Recommended Phase 2 Dose (RP2D)
timeFrame: Up to Part 1 Day 84 (Cycle 3, Day 28) (approximately 84 days)
measure: Number of participants with Objective Response
timeFrame: up to Month 12
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: up to Month 12
measure: Time to Progression (TTP)
timeFrame: up to Month 12
measure: Disease Control Rate (DCR)
timeFrame: up to Month 12
measure: Progression-free Survival
timeFrame: up to Month 12
measure: Maximum Observed Plasma Concentration of JNJ-42756493 (erdafitinib)
timeFrame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
measure: Time of Maximum Observed Plasma Concentration of JNJ-42756493 (erdafitinib)
timeFrame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
timeFrame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
measure: Half life of JNJ-42756493 (erdafitinib)
timeFrame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
measure: Apparent Volume of Distribution at Steady-State of JNJ-42756493 (erdafitinib)
timeFrame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
measure: Total Clearance of JNJ-42756493 (erdafitinib)
timeFrame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
measure: Accumulation Index of JNJ-42756493 (erdafitinib)
timeFrame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
measure: Duration of Objective Response (DOR)
timeFrame: Up to Month 12
Other outcomes:
Locations:
city: Changchun
country: China
city: Guangzhou
country: China
city: Hangzhou
country: China
city: Harbin
country: China
city: Nanjing
country: China
city: Shanghai
country: China
city: Seoul
country: Korea, Republic of
city: Kaohsiung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: