An Efficacy and Safety Study of Erdafitinib (JNJ-42756493) in Participants With Urothelial Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02365597|
Recruitment Status : Recruiting
First Posted : February 19, 2015
Last Update Posted : June 21, 2022
|Condition or disease||Intervention/treatment||Phase|
|Urothelial Cancer||Drug: Erdafitinib Drug: Midazolam Drug: Metformin||Phase 2|
Expanded Access : An investigational treatment associated with this study has been approved for sale to the public. More info ...
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||236 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2, Two-arm Multicenter, Open-Label Study to Determine the Efficacy and the Safety of Two Different Dose Regimens of a Pan-FGFR Tyrosine Kinase Inhibitor JNJ-42756493 in Subjects With Metastatic or Surgically Unresectable Urothelial Cancer With FGFR Genomic Alterations|
|Actual Study Start Date :||April 22, 2015|
|Estimated Primary Completion Date :||June 30, 2022|
|Estimated Study Completion Date :||June 30, 2022|
Experimental: Erdafitinib (8 milligram)
Prior to interim analysis 1 (IA1), there were 2 treatment regimens: Regimen 1 (10 milligram [mg] once daily, 7 days on/7 days off); and Regimen 2 (6 mg once daily for 28 days). Following IA1, Regimen 1 is closed for further enrollment and starting dose of Regimen 2 is increased to 8 mg once daily for 28 days on a 28-day cycle (referred to as Regimen 3). Participants who enrolled in DDI substudy will receive pretreatment with single doses of midazolam (Day -2) and metformin (Day -1). Participants will receive 8 mg erdafitinib treatment from Day 1 to Day 15, single doses of midazolam 2.5 mg (Day 13) and metformin 1000 mg (Day 14) and erdafitinib treatment will continued until disease progression.
8 mg orally once daily for 28 days on a 28 day cycle.
Other Name: JNJ-42756493
Participants who enrolled in DDI substudy will receive pretreatment with single dose of midazolam on Day -2 and single dose of midazolam on Day 13.
Participants who enrolled in DDI substudy will receive pretreatment with single dose of metformin on Day -1 and single dose of metformin on Day 14.
- Percentage of Participants with Best Overall Response [ Time Frame: From the start of the study treatment until the end of treatment (1 year) ]The objective response rate is defined as the percentage of participants with measurable lesions achieving a Complete Response (CR) or Partial Response (PR) based on Response Evaluation Criteria In Solid Tumors Version 1.1(RECIST v1.1) criteria. Per RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), greater than or equal to (>=) 30 percent (%) decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
- Progression-free survival [ Time Frame: From the date of the first dose of study drug until disease progression or death as assessed up to the last efficacy assessment for disease progression (up to 5 years) ]Progression-free survival is defined as the duration from the date of the first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience a complete response during the study) or death, whichever comes first.
- Duration of Response [ Time Frame: From the date of the first dose of study drug until disease progression or death as assessed up to the last efficacy assessment for disease progression (up to 5 years) ]The duration of response (CR or PR) is defined as the earliest date a participant achieved a complete response (CR) or a partial response (PR), calculated from the date of initial documentation of a response to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death.
- Overall survival [ Time Frame: From the date of the first dose of study drug until death (up to 5 years) ]Overall survival is defined as the time interval in days between the date of the first dose of study drug and the participant's death from any cause. If the participant is alive or the vital status is unknown, the participant's data will be censored at the date the participant was last known to be alive.
- Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Screening up to end of study (up to 5 years) ]An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
- Percentage of Participants With Biomarker Assessment [ Time Frame: Baseline up to end of study (up to 5 years) ]Presence of circulating biomarkers (DNA, RNA, or proteins) associated with FGFR aberrations will be observed.
- Plasma Concentration of Erdafitinib [ Time Frame: Baseline up to end of study (up to 5 years) ]
- Plasma Clearance of Erdafitinib [ Time Frame: Baseline up to end of study (up to 5 years) ]
- Volume of Distribution of Erdafitinib [ Time Frame: Baseline up to end of study (up to 5 years) ]
- Plasma Concentration of Midazolam and its Metabolite (1-OH-midazolam) [ Time Frame: Up to 14 days ]
- Plasma Concentration of Metformin [ Time Frame: Up to 15 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02365597
|Contact: Study Contact||Participate-In-This-Study@its.jnj.com|
|Study Director:||Janssen Research & Development, LLC Clinical Trial||Janssen Research & Development, LLC|