Description:
The purpose of this study is to evaluate the objective response rate (complete response [CR]+
partial response [PR]) of the selected dose regimen in participants with metastatic or
surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations.
Title
- Brief Title: An Efficacy and Safety Study of Erdafitinib (JNJ-42756493) in Participants With Urothelial Cancer
- 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
Clinical Trial IDs
- ORG STUDY ID:
CR105065
- SECONDARY ID:
42756493BLC2001
- SECONDARY ID:
2014-002408-26
- NCT ID:
NCT02365597
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Erdafitinib | JNJ-42756493 | Erdafitinib (8 milligram) |
| Midazolam | | Erdafitinib (8 milligram) |
| Metformin | | Erdafitinib (8 milligram) |
Purpose
The purpose of this study is to evaluate the objective response rate (complete response [CR]+
partial response [PR]) of the selected dose regimen in participants with metastatic or
surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations.
Detailed Description
This is a multicenter, open-label study (participants will know the identity of study drugs
administered) to evaluate the efficacy and safety of erdafitinib in participants with
urothelial cancer. The study comprises a 30-days Screening Phase, a Treatment Phase comprised
of 28-day treatment cycles that will continue until disease progression or unacceptable
toxicity occurs, and a post-treatment Follow-up Phase that will extend from the
End-of-Treatment Visit until the participant has died, withdraws consent, is lost to
follow-up, or the end of the study, whichever comes first. The end of study is defined as the
date when all participants have completed the study treatment (Regimens 1 to 3) or until the
last participant enrolled under the drug-drug interaction (DDI) substudy completes the end of
treatment visit,(whichever happens last). The purpose of DDI sub-study is to evaluate the
interaction of repeated doses of erdafitinib with a sensitive cytochrome 450 (CYP) 3A
substrate (midazolam) and with an organic cation transporter 2 (OCT2) probe substrate
(metformin). Safety will be monitored throughout the study.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Erdafitinib (8 milligram) | Experimental | 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. | - Erdafitinib
- Midazolam
- Metformin
|
Eligibility Criteria
Inclusion Criteria:
- Must have histologic demonstration of metastatic or surgically unresectable urothelial
cancer. Minor components of variant histology such as glandular or squamous
differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or
micropapillary change are acceptable
- Must have measurable disease according to the Response Evaluation Criteria in Solid
Tumors (RECIST, version 1.1) at baseline
- Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1,
or 2
- Must have adequate bone marrow, liver, and renal function as described in protocol
- Negative pregnancy test (urine or serum beta human chorionic gonadotropin [b-hCG]) at
Screening for women of child bearing potential who are sexually active
- Must have shown disease progression according to RECIST, version 1.1, following prior
chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants
who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or
progression according to RECIST, version 1.1, within 12 months of the last dose are
considered to have received chemotherapy in the metastatic setting. These participants
will be referred to as chemo-refractory participants. (Participants who have shown
disease progression according to RECIST, version 1.1 following prior treatment with
anti-Programmed death-ligand 1 (anti PDL1/PD1) antibodies are also eligible) For DDI
substudy
- Disease progression following prior chemotherapy for metastatic or surgically
unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant
chemotherapy and showed disease recurrence or progression within 12 months of the last
dose are considered to have received chemotherapy in the metastatic setting.
Exclusion Criteria:
- Received 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. Localized palliative radiation therapy (but should
not include radiation to target lesions) and ongoing bisphosphonates and denosumab,
are permitted
- Has persistent phosphate level greater than upper limit of normal (ULN) during
screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical
management
- Has a history of or current uncontrolled cardiovascular disease
- Females who are pregnant, breast-feeding, or planning to become pregnant within 3
months after the last dose of study drug and males who plan to father a child while
enrolled in this study or within 5 months after the last dose of study drug
- Has not recovered from reversible toxicity of prior anticancer therapy (except
toxicities which are not clinically significant such as alopecia, skin discoloration,
or Grade 1 neuropathy)
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Percentage of Participants with Best Overall Response |
| Time Frame: | From the start of the study treatment until the end of treatment (1 year) |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall survival |
| Time Frame: | From the date of the first dose of study drug until death (up to 5 years) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| Time Frame: | Screening up to end of study (up to 5 years) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Percentage of Participants With Biomarker Assessment |
| Time Frame: | Baseline up to end of study (up to 5 years) |
| Safety Issue: | |
| Description: | Presence of circulating biomarkers (DNA, RNA, or proteins) associated with FGFR aberrations will be observed. |
| Measure: | Plasma Concentration of Erdafitinib |
| Time Frame: | Baseline up to end of study (up to 5 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Plasma Clearance of Erdafitinib |
| Time Frame: | Baseline up to end of study (up to 5 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Volume of Distribution of Erdafitinib |
| Time Frame: | Baseline up to end of study (up to 5 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Plasma Concentration of Midazolam and its Metabolite (1-OH-midazolam) |
| Time Frame: | Up to 14 days |
| Safety Issue: | |
| Description: | |
| Measure: | Plasma Concentration of Metformin |
| Time Frame: | Up to 15 days |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Janssen Research & Development, LLC |
Trial Keywords
- Urothelial Cancer
- JNJ-42756493
- Erdafitinib
- Tyrosine Kinase Inhibitor
Last Updated
August 13, 2021
