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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort 1: Erdafitinib 		Participants with high-risk non-muscle-invasive bladder cancer (NMIBC) presenting as papillary tumor only (carcinoma in situ [CIS], absent), with disease recurrence after bacillus Calmette- Guerin (BCG) therapy will receive treatment with erdafitinib.
  • Drug: Erdafitinib
    Participants will receive erdafitinib orally beginning on Cycle 1 Day 1 until 2 years of treatment have been completed, disease recurrence, intolerable toxicity, withdrawal of consent, a decision by the investigator to discontinue treatment, or study termination, whichever occurs first. Each cycle is of 28 days.
    Other names:
    • JNJ-42756493
Active Comparator
Cohort 1: Investigators Choice 		Participants with high-risk NMIBC presenting as papillary tumor only (CIS, absent), with disease recurrence after BCG therapy will receive the investigator's choice of either intravesical gemcitabine or intravesical mitomycin C (MMC) or hyperthermic MMC. Participants who are randomized to gemcitabine or MMC or hyperthermic MMC in Cohort 1 and demonstrate a recurrence via investigator disease assessment will have the opportunity to cross over to treatment with erdafitinib.
  • Drug: Investigator Choice (Gemcitabine)
    Investigator's Choice treatment will be given once weekly for at least 4 doses of induction followed by monthly maintenance for at least 6 months.
  • Drug: Investigator Choice (Mitomycin C)
    Investigator's Choice treatment will be given once weekly for at least 4 doses of induction followed by monthly maintenance for at least 6 months.
Experimental
Cohort 2 		Participants with high-risk, BCG- unresponsive NMIBC presenting as CIS with or without concurrent papillary tumor will receive treatment with erdafitinib.
  • Drug: Erdafitinib
    Participants will receive erdafitinib orally beginning on Cycle 1 Day 1 until 2 years of treatment have been completed, disease recurrence, intolerable toxicity, withdrawal of consent, a decision by the investigator to discontinue treatment, or study termination, whichever occurs first. Each cycle is of 28 days.
    Other names:
    • JNJ-42756493
Experimental
Cohort 3 		Marker lesion study in intermediate-risk NMIBC presenting as papillary disease only. All enrolled participants will receive treatment with erdafitinib.
  • Drug: Erdafitinib
    Participants will receive erdafitinib orally beginning on Cycle 1 Day 1 until 2 years of treatment have been completed, disease recurrence, intolerable toxicity, withdrawal of consent, a decision by the investigator to discontinue treatment, or study termination, whichever occurs first. Each cycle is of 28 days.
    Other names:
    • JNJ-42756493

More Details

Status
Active, not recruiting
Sponsor
Janssen Research & Development, LLC

Study Contact

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.