Carcinoma, HepatocellularPhase 1/2NCT02421185
Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-42756493 (Erdafitinib) in Participants With Advanced Hepatocellular Carcinoma
A Phase 1/2 study testing JNJ-42756493 (erdafitinib) in people with Carcinoma, Hepatocellular, run by Janssen Research & Development, LLC at 10 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- JNJ-42756493 (erdafitinib)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 25 May 2015to 16 May 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
China6 sites
Study site
Changchun
Study site
Guangzhou
Study site
Hangzhou
Study site
Harbin
Study site
Nanjing
Study site
Shanghai
About this study
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
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.
Read the 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
- Being tested
- JNJ-42756493 (erdafitinib)
- Keywords
- Carcinoma, Hepatocellular, JNJ 42756493, a pan-Fibroblast Growth Factor Receptor Tyrosine Kinase Inhibitor
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JNJ-42756493 (erdafitinib)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.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Dose Escalation and Part 2: Dose Expansion | Experimental | 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. Receives: Drug: JNJ-42756493 (erdafitinib) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1:Recommended Phase 2 Dose (RP2D)
RP2D will be determined based on pharmacodynamics, biomarker response or clinical response, as well as the incidence rate and nature of the toxicities observed.
Measured: Up to Part 1 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Number of participants with Objective Response
Objective response based on assessment of confirmed Complete response (CR) or partial response (PR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.
Measured: up to Month 12
Secondary outcomes (12)
Number of Participants With Adverse Events
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Measured: up to Month 12
Time to Progression (TTP)
Time interval in months between the date of randomization and the date of disease progression or death due to progression, whichever occurred first.
Measured: up to Month 12
Disease Control Rate (DCR)
DCR defined as the proportion of participants with complete response [CR], partial response [PR], or stable disease [SD]), and duration of objective response (DOR).
Measured: up to Month 12
Progression-free Survival
Time from date of randomization to date of first documentation of objective tumor progression or death due to any cause, whichever occurred first.
Measured: up to Month 12
Maximum Observed Plasma Concentration of JNJ-42756493 (erdafitinib)
Measured: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Time of Maximum Observed Plasma Concentration of JNJ-42756493 (erdafitinib)
Measured: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
Measured: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Half life of JNJ-42756493 (erdafitinib)
Measured: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Apparent Volume of Distribution at Steady-State of JNJ-42756493 (erdafitinib)
Measured: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Total Clearance of JNJ-42756493 (erdafitinib)
Measured: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Accumulation Index of JNJ-42756493 (erdafitinib)
Measured: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Duration of Objective Response (DOR)
Measured: Up to Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2015 (estimated)
- Study start25 May 2015
- Primary completion13 May 2019
- Study completion16 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02421185
- Sponsor's protocol ID
- CR106971
- Other IDs
- 42756493HCC1001
- Status last verified
- Jan 2025
- First submitted
- 15 Apr 2015
- Last updated
- 3 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02421185
- Acronym / sponsor ID
- CR106971
- Conditions
- Carcinoma, Hepatocellular
- Keywords
- Carcinoma, Hepatocellular, JNJ 42756493, a pan-Fibroblast Growth Factor Receptor Tyrosine Kinase Inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 25 May 2015 (actual)
- Primary completion
- 13 May 2019 (actual)
- Study completion
- 16 May 2019 (actual)
- First posted
- 20 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Part 1: Dose Escalation and Part 2: Dose Expansion | Experimental | Drug: JNJ-42756493 (erdafitinib)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Part 1: Dose Escalation and Part 2: Dose Expansion |
Primary outcome
Part 1:Recommended Phase 2 Dose (RP2D)
Time frame: Up to Part 1 Day 84 (Cycle 3, Day 28) (approximately 84 days)
RP2D will be determined based on pharmacodynamics, biomarker response or clinical response, as well as the incidence rate and nature of the toxicities observed.
Number of participants with Objective Response
Time frame: up to Month 12
Objective response based on assessment of confirmed Complete response (CR) or partial response (PR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.
12 secondary outcomes
Number of Participants With Adverse Events
Time frame: up to Month 12
Time to Progression (TTP)
Time frame: up to Month 12
Disease Control Rate (DCR)
Time frame: up to Month 12
Progression-free Survival
Time frame: up to Month 12
Maximum Observed Plasma Concentration of JNJ-42756493 (erdafitinib)
Time frame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Time of Maximum Observed Plasma Concentration of JNJ-42756493 (erdafitinib)
Time frame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Time frame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Half life of JNJ-42756493 (erdafitinib)
Time frame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Apparent Volume of Distribution at Steady-State of JNJ-42756493 (erdafitinib)
Time frame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Total Clearance of JNJ-42756493 (erdafitinib)
Time frame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Accumulation Index of JNJ-42756493 (erdafitinib)
Time frame: Up to Part 2 Day 84 (Cycle 3, Day 28) (approximately 84 days)
Duration of Objective Response (DOR)
Time frame: Up to Month 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2025.
- 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)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing JNJ-42756493 (erdafitinib) in people with Carcinoma, Hepatocellular, run by Janssen Research & Development, LLC at 10 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in China, Taiwan, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1:Recommended Phase 2 Dose (RP2D) (time frame: Up to Part 1 Day 84 (Cycle 3, Day 28) (approximately 84 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.