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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)

NCT04172675

Description:

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.

Related Conditions:
  • Bladder Papillary Urothelial Carcinoma
  • Stage 0is Bladder Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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)
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CR108699
  • SECONDARY ID: 2019-002449-39
  • SECONDARY ID: 42756493BLC2003
  • NCT ID: NCT04172675

Conditions

  • Urinary Bladder Neoplasms

Interventions

DrugSynonymsArms
ErdafitinibJNJ-42756493Cohort 1: Erdafitinib
Investigator Choice (Gemcitabine)Cohort 1: Investigators Choice
Investigator Choice (Mitomycin C)Cohort 1: Investigators Choice

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.

Detailed Description

      This study enrolls participants with high risk NMIBC 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 MMC/hyperthermic MMC).
      The study consists of Screening period, Treatment Phase and Follow-up Phase.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: ErdafitinibExperimentalParticipants 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.
  • Erdafitinib
Cohort 1: Investigators ChoiceActive ComparatorParticipants 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)/hyperthermic MMC. Participants who are randomized to gemcitabine or MMC/hyperthermic MMC in Cohort 1 and demonstrate a recurrence via investigator disease assessment will have the opportunity to cross over to treatment with erdafitinib.
  • Investigator Choice (Gemcitabine)
  • Investigator Choice (Mitomycin C)
Cohort 2ExperimentalParticipants with high-risk, BCG- unresponsive NMIBC presenting as CIS with or without concurrent papillary tumor will receive treatment with erdafitinib.
  • Erdafitinib
Cohort 3ExperimentalMarker lesion study in intermediate-risk NMIBC presenting as papillary disease only. All enrolled participants will receive treatment with erdafitinib.
  • Erdafitinib

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-hCG
             [beta-human chorionic gonadotropin]) (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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recurrence-Free Survival (RFS)
Time Frame:Up to 4 years
Safety Issue:
Description:RFS is defined as the time from the date of randomization until the date of the reappearance of high-risk disease, or death, whichever is reported first.

Secondary Outcome Measures

Measure:Time to Progression
Time Frame:Up to 4 years
Safety Issue:
Description:Time from the date of randomization until the date of first documented evidence of any of progression or death. Participants who are progression -free and alive or have unknown status will be censored at the date of the last tumor assessment.
Measure:Time to Disease Worsening
Time Frame:Up to 4 years
Safety Issue:
Description:Time from the date of randomization to the date of first documented evidence of change in therapy indicative of more advanced disease. Participants who are free of disease worsening and alive or have unknown status will be censored at the last tumor assessment.
Measure:Disease-Specific Survival
Time Frame:Up to 4 years
Safety Issue:
Description:The time from the date of randomization to the date of the participant's death resulting from bladder cancer. Participants who are alive or have unknown vital status will be censored at the date the participant was last known to be alive. Participants whose death result from causes other than bladder cancer will be censored at their death dates.
Measure:Overall Survival
Time Frame:Up to 4 years
Safety Issue:
Description:The time from the date of randomization to the date of the participant's death resulting from any cause. Participants who are alive or have unknown vital status will be censored at the date the participant was last known to be alive.
Measure:Recurrence-Free Survival
Time Frame:Months 6, 12, and 24
Safety Issue:
Description:RFS is defined as the time from the date of randomization until the date of the reappearance of high-risk disease, or death, whichever is reported first. Participants who are recurrence-free and alive or have unknown status will be censored at the last tumor assessment.
Measure:Recurrence-Free Survival 2 (RFS2)
Time Frame:Up to 4 years
Safety Issue:
Description:RFS2 is defined as the time from the date of randomization until the date of the reappearance of high-risk disease on the first subsequent non-surgical anticancer treatment, or death, whichever is reported first.
Measure:RFS by Central Histopathologic Review
Time Frame:Up to 4 years
Safety Issue:
Description:RFS will be assessed by central histopathologic review. RFS is defined as the time from the date of randomization until the date of the reappearance of high-risk disease, or death, whichever is reported first.
Measure:Plasma Concentration of Erdafitinib
Time Frame:Cycle 1 Day 14, Cycle 2 Day 1 (each cycle is of 28 days)
Safety Issue:
Description:Plasma concentration of erdafitinib will be reported.
Measure:Number of Participants with Adverse events
Time Frame:Up to 4 years
Safety Issue:
Description: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
Measure:Change from Baseline in Patient's Global Impression of Severity (of cancer) (PGIS)
Time Frame:Baseline up to 4 years
Safety Issue:
Description:PGIS is single-item questionnaires to evaluate patient's global impression of severity.
Measure:Change from Baseline in Patient's Global Impression of Change (of cancer) (PGIC)
Time Frame:Baseline, Cycle 2 Day 1 and end of treatment (up to 2 years) (each cycle is of 28 days)
Safety Issue:
Description:PGIC is single-item questionnaires to evaluate a patient's global impression of change of cancer.
Measure:Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) -C30
Time Frame:Baseline up to 4 years
Safety Issue:
Description:EORTC QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies.
Measure:Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24
Time Frame:Baseline up to 4 years
Safety Issue:
Description:EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with superficial (non-muscle-invasive) bladder cancer. The questionnaire is designed to supplement the QLQ-C30.
Measure:Change from Baseline in EuroQol European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L)
Time Frame:Baseline up to 4 years
Safety Issue:
Description:EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression.
Measure:Maximum Observed Analyte Concentration (Cmax) of Midazolam and its Metabolite (1-OH-Midazolam)
Time Frame:Predose, Cycle 1 Day 13 (each cycle is of 28 days)
Safety Issue:
Description:Cmax is the maximum observed analyte concentration.
Measure:Time to Reach Maximum Observed Analyte Concentration (Tmax) Midazolam and its Metabolite (1-OH-Midazolam)
Time Frame:Predose, Cycle 1 Day 13 (each cycle is of 28 days)
Safety Issue:
Description:Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Measure:Area Under the Analyte Concentration Versus time Curve (AUC) from Time Zero to the Time of Last Measurable Analyte Concentration of Midazolam and its Metabolite (1-OH-Midazolam)
Time Frame:Predose, Cycle 1 Day 13 (each cycle is of 28 days)
Safety Issue:
Description:AUClast defined as time zero to the time of the last measurable (non-below quantification limit [BQL]) analyte concentration.
Measure:Area Under the Analyte Concentration Versus time Curve (AUC) from Time Zero to Infinite Time of Midazolam and its Metabolite (1-OH-Midazolam)
Time Frame:Predose, Cycle 1 Day 13 (each cycle is of 28 days)
Safety Issue:
Description:AUCinfinity is defined as time zero to infinite time.
Measure:Maximum Observed Plasma Concentration (Cmax) of Metformin
Time Frame:Predose, Cycle 1 Day 14 (each cycle is of 28 days)
Safety Issue:
Description:Cmax is the maximum observed analyte concentration.
Measure:Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin
Time Frame:Predose, Cycle 1 Day 14 (each cycle is of 28 days)
Safety Issue:
Description:Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
Measure:Area Under the Analyte Concentration Versus time Curve (AUC) from Time Zero to the Time of Last Measurable of Metformin
Time Frame:Predose, Cycle 1 Day 14 (each cycle is of 28 days)
Safety Issue:
Description:AUClast defined as time zero to the time of the last measurable (non-below quantification limit [BQL]) analyte concentration
Measure:Area Under the Analyte Concentration Versus time Curve (AUC) from Time Zero to Infinite Time of Metformin
Time Frame:Predose, Cycle 1 Day 14 (each cycle is of 28 days)
Safety Issue:
Description:AUCinfinity is defined as time zero to infinite time.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Janssen Research & Development, LLC

Trial Keywords

  • Non muscle invasive bladder cancer (NMIBC)
  • Bacillus calmette- guerin (BCG) failure
  • BCG unresponsive

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