Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-42756493 (Erdafitinib) in Participants With Advanced Hepatocellular Carcinoma

NCT ID: NCT02421185

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-25
• Study Completion Date: 2019-05-16

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.

Conditions

Carcinoma, Hepatocellular

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Dose Escalation and Part 2: Dose Expansion

Part 1: First, participants will receive 8 milligram (mg) (starting dose) tablet of JNJ-42756493 (erdafitinib) orally once daily from Day 1 to 7, then Day 15 to 21 of 28 days cycle or 8 mg orally once daily from Day 1 to 21 of 28 days cycle (intermittent dosing). After recommended Phase 2 dose (RP2D) is identified, enrollment of continuous dosing schedule will be open, starting at 8mg. In this cohort, participants will receive 8mg (starting dose) tablet of JNJ42756493 (erdafitinib) orally once daily from Day 1 to Day 28 in a 28-day cycle. Dose of the study medication will be escalated sequentially till the dose limiting toxicity is achieved to determine RP2D.

Part 2: Participants will receive RP2D JNJ-42756493 (erdafitinib) dose determined in Part 1. Participants who are tolerating study drug treatment and achieve clinical responses or stable disease will continue to receive study drug at the same dose until disease progression, unacceptable toxicity, or withdrawal of consent.

Group Type: EXPERIMENTAL

JNJ-42756493 (erdafitinib)

Intervention Type: DRUG

Part 1: Participants will receive 8 mg tablet once daily from Day 1 to 7, and then Day 15 to 21 of 28 days cycle or 8 mg orally once daily of 28 days cycle up to the maximum tolerated dose in order to determine the recommended Phase 2 dose.

Part 2: Recommended Phase 2 JNJ-42756493 (erdafitinib) dose determined in Part 1.

Interventions

JNJ-42756493 (erdafitinib)

Part 1: Participants will receive 8 mg tablet once daily from Day 1 to 7, and then Day 15 to 21 of 28 days cycle or 8 mg orally once daily of 28 days cycle up to the maximum tolerated dose in order to determine the recommended Phase 2 dose.

Part 2: Recommended Phase 2 JNJ-42756493 (erdafitinib) dose determined in Part 1.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Changchun, , China

Guangzhou, , China

Hangzhou, , China

Harbin, , China

Nanjing, , China

Shanghai, , China

Seoul, , South Korea

Kaohsiung City, , Taiwan

Tainan City, , Taiwan

Taipei, , Taiwan

Countries

China; South Korea; Taiwan

Related Links

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR106971&attachmentIdentifier=a83f6736-1bf3-4f4f-8db2-b6dcfbce350e&fileName=CR106971_CSR_Synopsis.pdf&versionIdentifier=

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 (HCC)

Other Identifiers

42756493HCC1001

Identifier Type: OTHER

Identifier Source: secondary_id

CR106971

Identifier Type: -

Identifier Source: org_study_id