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A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations

NCT03390504

Description:

The purpose of this study is to evaluate efficacy of erdafitinib versus chemotherapy or pembrolizumab in participants with advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations who have progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-PD-(L) 1 agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2).

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations
  • Official Title: A Phase 3 Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects With Advanced Urothelial Cancer and Selected FGFR Gene Aberrations

Clinical Trial IDs

  • ORG STUDY ID: CR108401
  • SECONDARY ID: 2017-002932-18
  • SECONDARY ID: 42756493BLC3001
  • NCT ID: NCT03390504

Conditions

  • Urothelial Cancer

Interventions

DrugSynonymsArms
ErdafitinibJNJ-42756493Cohort 1 (Arm 1A): Erdafitinib
VinflunineCohort 1 (Arm 1B): Vinflunine or Docetaxel
DocetaxelCohort 1 (Arm 1B): Vinflunine or Docetaxel
PembrolizumabCohort 2 (Arm 2B): Pembrolizumab

Purpose

The purpose of this study is to evaluate efficacy of erdafitinib versus chemotherapy or pembrolizumab in participants with advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations who have progressed after one prior treatment.

Detailed Description

      A study of erdafitinib versus standard of care, consisting of chemotherapy (docetaxel or
      vinflunine) or PD1 agent pembrolizumab, in participants with advanced urothelial cancer and
      selected FGFR aberrations who have progressed on or after one prior line of systemic therapy.
      It will consist of screening, treatment phase (from randomization until disease progression,
      intolerable toxicity, withdrawal of consent or decision by investigator to discontinue
      treatment else participants will discontinue treatment after completion of 2 years
      pembrolizumab therapy), post-treatment follow-up (from end-of-treatment to participants
      death, withdraws consent, lost to follow-up, or end of study, whichever comes first).
      Efficacy, pharmacokinetics, biomarkers, patient reported outcomes, medical resource
      utilization and safety will be assessed.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 (Arm 1A): ErdafitinibExperimentalParticipants will be screened based on Fibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA) to determine molecular eligibility and participants who meet molecular eligibility criteria will be enrolled. Participants (treated with prior anti-anti-programmed cell death protein [PD][L]1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 milligram (mg), once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustment are based on phosphate level and observed toxicity (adverse events [AEs]).
  • Erdafitinib
Cohort 1 (Arm 1B): Vinflunine or DocetaxelExperimentalParticipants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be enrolled. Participants (treated with prior anti-PD[L]1 agent) will receive vinflunine 320 milligram per meter square (mg/m^2) as a 20-minute intravenous infusion once every 3 weeks or docetaxel 75 mg/m^2 as a 1 hour intravenous infusion every 3 weeks. Treatment with either agent (choice of investigator) will be administered until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities.
  • Vinflunine
  • Docetaxel
Cohort 2 (Arm 2A): ErdafitinibExperimentalParticipants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be enrolled. Participants (no prior treatment with anti-PD(L)1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 mg, once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on phosphate level and observed toxicity (AEs).
  • Erdafitinib
Cohort 2 (Arm 2B): PembrolizumabExperimentalParticipants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be enrolled. Participants (no prior treatment with anti-PD(L)1 agent) will receive pembrolizumab 200 mg as a 30-minute intravenous infusion once every 3 weeks, until disease progression, intolerable toxicity, withdrawal of consent, decision by the investigator to discontinue treatment or the completion of 2 years of pembrolizumab therapy. Dose adjustments are based on observed toxicities.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologic demonstration of transitional cell carcinoma of the urothelium. Minor
             components ( less than [<] 50 percent [%] overall) of variant histology such as
             glandular or squamous differentiation, or evolution to more aggressive phenotypes such
             as sarcomatoid or micropapillary change are acceptable

          -  Stage IV disease (metastatic or surgically unresectable, cT4b, N+, or M+ cancer)

          -  Documented progression of disease, defined as any progression that requires a change
             in treatment, prior to randomization

          -  Only one line of prior systemic treatment for metastatic urothelial cancer.
             Participants who received neoadjuvant or adjuvant chemotherapy and showed disease
             progression (as defined above), within 12 months of the last dose are considered to
             have received systemic chemotherapy in the metastatic setting Cohort 1: prior
             chemotherapy and anti-PD(L)1 [in combination or in maintenance setting] (anti-PD(L)1
             alone is allowed only for participants with documented cisplatin ineligibility) and
             Cohort 2: prior chemotherapy (no prior anti-PD(L)1 treatment)

          -  A woman of childbearing potential who is sexually active must have a negative
             pregnancy test (beta human chorionic gonadotropin [beta hCG]) at Screening (urine or
             serum)

          -  Participants must meet appropriate molecular eligibility criteria

          -  Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2

          -  Adequate bone marrow, liver, and renal function

        Exclusion Criteria:

          -  Treatment with any other investigational agent or participation in another clinical
             study with therapeutic intent within 30 days prior to randomization

          -  Active malignancies (that is, requiring treatment change in the last 24 months) other
             than urothelial cancer (except skin cancers within the last 24 months that is
             considered completely cured)

          -  Symptomatic central nervous system metastases

          -  Received prior fibroblast growth factor receptor (FGFR) inhibitor treatment

          -  Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients

          -  Corneal or retinal abnormality likely to increase the risk of eye toxicity

          -  History of uncontrolled cardiovascular disease including

          -  Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers,
             known gastric ulcers, or unhealed incisions
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Date of first randomization to the date of participant's death (approximately up to 3 years)
Safety Issue:
Description:Overall survival is measured from the date of randomization to the date of the participant's death. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant was last known to be alive.

Secondary Outcome Measures

Measure:Progression-free Survival (PFS)
Time Frame:Date of randomization to the date of disease progression or relapse from complete response (CR) or death, whichever is reported first (approximately up to 3 years)
Safety Issue:
Description:PFS is defined as duration in days from date of randomization to disease progression date (assessed per Response Evaluation Criteria in Solid Tumors Version 1.1 [RECIST v1.1] by investigator) or relapse from CR or death, whichever is reported first. RECIST 1.1, progressive disease is defined as a 20 percent (%) increase in the sum of diameters of all target lesions and a minimum absolute increase of 5 millimeter (mm) in the sum. CR is defined as disappearance of all target lesions, non-target lesions and normalization of tumor marker level.
Measure:Overall Response Rate (ORR)
Time Frame:Approximately up to 3 years
Safety Issue:
Description:ORR is defined as the proportion of participants who achieve CR (CR; disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), as assessed per RECIST v1.1 by the investigator.
Measure:Time to Worsening in Symptom Items and Functioning Subscales in Patient-Reported Health Status of the Functional Assessment of Cancer Therapy-Bladder Cancer (FACT-Bl)
Time Frame:Baseline up to end of treatment (approximately 3 years)
Safety Issue:
Description:The FACT-Bl consists of 36 core items, with 5-point Likert response scales, covering 5 primary domains: Physical well-being, social/family well-being, emotional well-being, functional well-being and bladder symptom subscale. The answer scales range from "Not at all (score=0)" to "very much (score=4)" to assess the meaningful significant symptom deterioration.
Measure:Change from Baseline in Patient-Global Impression of Severity (PGIS) Score
Time Frame:Baseline up to end of treatment (approximately 3 years)
Safety Issue:
Description:The PGIS is a single question regarding the participant report of disease severity. Participants will be asked that ''considering all aspects of your bladder cancer symptoms right now, would you say your bladder cancer symptoms are none, mild, moderate, severe, or very severe?" The PGIS is an anchor question that will be used to establish the magnitude of meaningful change in this study by assessing disease severity.
Measure:Change from Baseline in the Visual Analog Scale (VAS) of the EQ-5D-5L
Time Frame:Baseline up to follow up phase (approximately 3 years)
Safety Issue:
Description:European Quality of Life 5 Dimensions (EQ-5D) visual analog scale (VAS) is a 20 centimeter (cm) vertical VAS with scores ranging from 0 (worst imaginable health) to 100 (perfect health). A higher score indicates an improvement in health in the Health Status Index.
Measure:Change from Baseline in the Utility Scale of the EQ-5D-5L
Time Frame:Baseline up to follow up phase (approximately 3 years)
Safety Issue:
Description:The EuroQol-5 is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead.
Measure:Duration of Response (DOR)
Time Frame:From the date of initial documentation of a response to date of first documented evidence of progressive disease (or participants relapse who experience CR during the study) or death (approximately up to 3 years)
Safety Issue:
Description:DOR for responders is defined as duration in days from the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) or relapse for participants who experience CR (CR; disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level) during the study or death.
Measure:Number of Participants with Adverse Events (AEs) as a Measure of Safety
Time Frame:Approximately up to 3 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.
Measure:Oral Clearance (CL/F) of Erdafitinib
Time Frame:Day 14 (Cycle 1), Day 1 (Cycle 2) (each cycle is of 21 days)
Safety Issue:
Description:CL/F is the oral clearance; that is clearance based on oral bioavailability of erdafitinib.
Measure:Area Under the Plasma Concentration-Time Curve from Time Zero to Time 't' (AUC[0-t]) of Erdafitinib
Time Frame:Day 14 (Cycle 1), Day 1 (Cycle 2) (each cycle is of 21 days)
Safety Issue:
Description:AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't' of erdafitinib.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

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