Brief Summary
The purpose of this study is to evaluate recurrence-free survival (RFS) in participants treated with erdafitinib vs Investigator's Choice, for participants with high-risk non-muscle-invasive bladder cancer (NMIBC) who harbor fibroblast growth factor receptor (FGFR) mutations or fusions, and who recurred after bacillus calmette-guerin (BCG) therapy.
Brief Title
A Study of Erdafitinib Versus Investigator Choice of Intravesical Chemotherapy in Participants Who Received Bacillus Calmette-Guérin (BCG) and Recurred With High Risk Non-Muscle-Invasive Bladder Cancer (NMIBC)
Detailed Description
This study enrolls participants with high risk NMIBC and FGFR mutations or fusions. Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) 1-4 inhibitor with demonstrated clinical activity in participants with solid tumors, including urothelial carcinoma, with alterations in the FGFR pathway. In Cohort 1, participants will be randomized to erdafitinib or to Investigators Choice (intravesical gemcitabine or intravesical mitomycin C \[MMC\] or hyperthermic MMC). The study consists of screening period, treatment phase, follow-up phase, and long-term extension phase.
Completion Date
Completion Date Type
Actual
Conditions
Urinary Bladder Neoplasms
Eligibility Criteria
Inclusion Criteria:
* Histologically confirmed, recurrent, non-muscle-invasive urothelial carcinoma of the bladder. Variant pathology are allowed
* Tumor with specified fibroblast growth factor receptor (FGFR) mutations or fusions
* Bacillus Calmette- Guerin (BCG)-unresponsive after adequate BCG therapy or BCG experienced participants
* Refuses or is not eligible for cystectomy (Cohort 1 and Cohort 2 only)
* Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-1
* Must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
* A woman of childbearing potential must have a negative pregnancy test (beta-human chorionic gonadotropin \[beta-hCG\]) (urine or serum) within 7 days before randomization (Cohort 1) or the first dose of study drug (Cohort 2 and Cohort 3)
* Adequate bone marrow, liver, and renal function as specified in the protocol
Exclusion Criteria:
* Histologically confirmed, muscle-invasive (T2 or higher stage) urothelial carcinoma of the bladder
* Histopathology demonstrating any small cell component, pure adenocarcinoma, pure squamous cell carcinoma, or pure squamous CIS of the bladder
* Prior treatment with an FGFR inhibitor
* Active malignancies other than the disease being treated under study. The only allowed exceptions are: (a) skin cancer treated within the last 24 months that is considered completely cured (b) adequately treated lobular carcinoma in situ (LCIS) and ductal CIS (c) history of localized breast cancer and receiving antihormonal agents, or history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy
* Current central serous retinopathy or retinal pigment epithelial detachment of any grade
* Histologically confirmed, recurrent, non-muscle-invasive urothelial carcinoma of the bladder. Variant pathology are allowed
* Tumor with specified fibroblast growth factor receptor (FGFR) mutations or fusions
* Bacillus Calmette- Guerin (BCG)-unresponsive after adequate BCG therapy or BCG experienced participants
* Refuses or is not eligible for cystectomy (Cohort 1 and Cohort 2 only)
* Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-1
* Must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
* A woman of childbearing potential must have a negative pregnancy test (beta-human chorionic gonadotropin \[beta-hCG\]) (urine or serum) within 7 days before randomization (Cohort 1) or the first dose of study drug (Cohort 2 and Cohort 3)
* Adequate bone marrow, liver, and renal function as specified in the protocol
Exclusion Criteria:
* Histologically confirmed, muscle-invasive (T2 or higher stage) urothelial carcinoma of the bladder
* Histopathology demonstrating any small cell component, pure adenocarcinoma, pure squamous cell carcinoma, or pure squamous CIS of the bladder
* Prior treatment with an FGFR inhibitor
* Active malignancies other than the disease being treated under study. The only allowed exceptions are: (a) skin cancer treated within the last 24 months that is considered completely cured (b) adequately treated lobular carcinoma in situ (LCIS) and ductal CIS (c) history of localized breast cancer and receiving antihormonal agents, or history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy
* Current central serous retinopathy or retinal pigment epithelial detachment of any grade
Inclusion Criteria
Inclusion Criteria:
* Histologically confirmed, recurrent, non-muscle-invasive urothelial carcinoma of the bladder. Variant pathology are allowed
* Tumor with specified fibroblast growth factor receptor (FGFR) mutations or fusions
* Bacillus Calmette- Guerin (BCG)-unresponsive after adequate BCG therapy or BCG experienced participants
* Refuses or is not eligible for cystectomy (Cohort 1 and Cohort 2 only)
* Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-1
* Must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
* A woman of childbearing potential must have a negative pregnancy test (beta-human chorionic gonadotropin \[beta-hCG\]) (urine or serum) within 7 days before randomization (Cohort 1) or the first dose of study drug (Cohort 2 and Cohort 3)
* Adequate bone marrow, liver, and renal function as specified in the protocol
* Histologically confirmed, recurrent, non-muscle-invasive urothelial carcinoma of the bladder. Variant pathology are allowed
* Tumor with specified fibroblast growth factor receptor (FGFR) mutations or fusions
* Bacillus Calmette- Guerin (BCG)-unresponsive after adequate BCG therapy or BCG experienced participants
* Refuses or is not eligible for cystectomy (Cohort 1 and Cohort 2 only)
* Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-1
* Must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
* A woman of childbearing potential must have a negative pregnancy test (beta-human chorionic gonadotropin \[beta-hCG\]) (urine or serum) within 7 days before randomization (Cohort 1) or the first dose of study drug (Cohort 2 and Cohort 3)
* Adequate bone marrow, liver, and renal function as specified in the protocol
Gender
All
Gender Based
false
Keywords
Non muscle invasive bladder cancer (NMIBC)
Bacillus calmette- guerin (BCG) failure
BCG unresponsive
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04172675
Org Class
Industry
Org Full Name
Janssen Research & Development, LLC
Org Study Id
CR108699
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized Phase 2 Study of Erdafitinib Versus Investigator Choice of Intravesical Chemotherapy in Subjects Who Received Bacillus Calmette-Guérin (BCG) and Recurred With High Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) and FGFR Mutations or Fusions
Primary Outcomes
Outcome Description
RFS was defined as the time from the date of randomization until the date of the reappearance of high-risk disease (high-grade Ta, T1 or carcinoma in situ \[CIS\]), or death, whichever was reported first. Recurrence was assessed using cystoscopy, bladder mapping, urine cytology, and computed tomography (CT)/ magnetic resonance imaging (MRI) urogram. Participants who were recurrence-free and alive or had unknown status were censored at the last tumor assessment. The Kaplan-Meier method was used to estimate the distribution of overall RFS for each treatment group.
Outcome Measure
Cohort 1: Recurrence-Free Survival (RFS)
Outcome Time Frame
From randomization (Cycle 1 Day 1, pre-dose) up to 48.2 months
Secondary Ids
Secondary Id
42756493BLC2003
Secondary Id
2019-002449-39
Secondary Id
2023-510306-40-00
Secondary Outcomes
Outcome Description
RFS rate was the proportion of participants who were recurrence-free and alive based on Kaplan-Meier estimates. RFS was defined as the time from the date of randomization until the date of the reappearance of high-risk disease (high-grade Ta, T1 or CIS), or death, whichever was reported first. Recurrence was assessed using cystoscopy, bladder mapping, urine cytology, and CT/ MRI urogram. Participants who were recurrence-free and alive or had unknown status were censored at the last tumor assessment.
Outcome Time Frame
At Month 6 and Month 12
Outcome Measure
Cohort 1: Recurrence-Free Survival Rate at 6 Months and 12 Months
Outcome Description
Time to progression (TTP) was defined as the time from the date of randomization until the date of first documented evidence of any of the following: disease progression (PD) or death. PD included development of or increase in stage to lamina propria invasion (for example- increase from Ta to T1), development of or increase in stage to muscle-invasive disease (stage greater than or equal to \[\>=\] T2), development of or increase in stage to lymph node (N+) or distant metastasis (M1) disease (participants must have previously been diagnosed with N0 and/or M0 disease), increase in tumor grade from low to high (including CIS).
Outcome Time Frame
From randomization (Cycle 1 Day 1, pre-dose) up to 48.2 months
Outcome Measure
Cohort 1: Time to Progression
Outcome Description
Overall survival was defined as the time from the date of randomization to the date of the participant's death due to any cause.
Outcome Time Frame
From randomization (Cycle 1 Day 1, pre-dose) up to 48.2 months
Outcome Measure
Cohort 1: Overall Survival
Outcome Description
An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were the events between first dose of study drug and up to 30 (+7 days) days after last dose or before start of subsequent anticancer therapy, whichever occurred first. All TEAEs including serious and non-serious events were reported in this outcome measure (OM).
Outcome Time Frame
From start of treatment (Day 1) up to 25.2 months
Outcome Measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Outcome Description
Plasma concentrations of erdafitinib were reported. Plasma samples were analyzed using liquid chromatography/mass spectrometry method.
Outcome Time Frame
All cohorts: Pre-dose on Cycle 1 Day 14, pre-dose and 3 hours post-dose on Cycle 2 Day 1 (each cycle was of 28 days)
Outcome Measure
Plasma Concentrations of Erdafitinib
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404
Categories Mesh Debug
Prostate Cancer --- UROGENITAL NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Kidney & Urinary Tract --- URINARY BLADDER DISEASES
Kidney & Urinary Tract --- UROLOGIC DISEASES
Cancer --- CARCINOMA
Lung & Chest Cancers --- NEOPLASMS, GLANDULAR AND EPITHELIAL
MeSH Terms
URINARY BLADDER NEOPLASMS
NON-MUSCLE INVASIVE BLADDER NEOPLASMS
UROLOGIC NEOPLASMS
UROGENITAL NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
FEMALE UROGENITAL DISEASES
FEMALE UROGENITAL DISEASES AND PREGNANCY COMPLICATIONS
UROGENITAL DISEASES
URINARY BLADDER DISEASES
UROLOGIC DISEASES
MALE UROGENITAL DISEASES
CARCINOMA
NEOPLASMS, GLANDULAR AND EPITHELIAL
NEOPLASMS BY HISTOLOGIC TYPE
ERDAFITINIB
GEMCITABINE
MITOMYCIN
HETEROCYCLIC COMPOUNDS
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
MITOMYCINS
INDOLEQUINONES
QUINONES
ORGANIC CHEMICALS
AZIRINES
INDOLES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING