Have you or your loved ones been diagnosed with urothelial cancer?

You may be eligible to participate in a urothelial cancer clinical trial.

Have you or your loved ones been diagnosed with urothelial cancer? You may be eligible to participate in a urothelial cancer clinical trial.

What is a clinical trial? Is participating in a clinical trial right for you? Learn more

Urothelial Cancer Clinical Trial

NCT03390504 | Phase 3 | Interventional

Have you or your loved ones been diagnosed with urothelial cancer?

You may be eligible to participate in a urothelial cancer clinical trial.

Have you or your loved ones been diagnosed with urothelial cancer? You may be eligible to participate in a urothelial cancer clinical trial.

Recruiting

Male & Female

18 Years +

This study is looking to recruit 631 Participants

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-programmed death ligand 1(PD-[L]1) agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2).

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Details for the study

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

Brief Summary

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

Detailed Description

A study of erdafitinib versus standard of care, consisting of chemotherapy (docetaxel or
vinflunine) or anti-PD-(L) 1 agent pembrolizumab, in participants with advanced urothelial
cancer and selected FGFR aberrations who have progressed on or 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). It will consist of screening, treatment phase
(from randomization until disease progression, intolerable toxicity, withdrawal of consent or
decision by investigator to discontinue treatment, post-treatment follow-up (from
end-of-treatment to participants death, withdraws consent, lost to follow-up study completion
for the respective cohort, whichever comes first). The study will have long term extension
(LTE) period after clinical cutoff date is achieved for final analysis of each cohort and
participants eligible in the opinion of the investigator, will continue to benefit from the
study intervention. Efficacy, pharmacokinetics, biomarkers, patient reported outcomes,
medical resource utilization and safety will be assessed.

Treatments and/or Procedures

Fibroblast growth factor receptor inhibitor clinical trial assay FGF ri CTA

FGFRi CTA will be used to determine molecular eligibility.

Docetaxel

Participants will receive docetaxel 75 mg/m^2 as a 1 hour intravenous infusion.

Pembrolizumab

Participants will receive pembrolizumab 200 mg as a 30-minute intravenous infusion.

Vinflunine

Participants will receive vinflunine 320 mg/m^2 as a 20-minute intravenous infusion.

Erdafitinib

Participants will swallow erdafitinib tablets orally at a starting dose of 8 mg.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

Primary

Overall Survival (OS)

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.

Date of first randomization to the date of participant's death (approximately up to 3 years)

Secondary

Area Under the Plasma Concentration-Time Curve from Time Zero to Time 't' (AUC[0-t]) of Erdafitinib

AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't' of erdafitinib.

Day 14 (Cycle 1), Day 1 (Cycle 2) (each cycle is of 21 days)

Secondary

Oral Clearance (CL/F) of Erdafitinib

CL/F is the oral clearance; that is clearance based on oral bioavailability of erdafitinib.

Day 14 (Cycle 1), Day 1 (Cycle 2) (each cycle is of 21 days)

Secondary

Number of Participants with Adverse Events (AEs) as a Measure of Safety

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.

Approximately up to 3 years

Secondary

Duration of Response (DOR)

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.

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)

Secondary

Change from Baseline in the Visual Analog Scale (VAS) of the EQ-5D-5L

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.

Baseline up to follow up phase (approximately 3 years)

Secondary

Change from Baseline in Patient-Global Impression of Severity (PGIS) Score

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.

Baseline up to end of treatment (approximately 3 years)

Secondary

Time Until Symptom Deterioration (Subset of FACT-BI Items)

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.

Baseline up to end of treatment (approximately 3 years)

Secondary

Change from Baseline in Participant-Reported Health Status and Physical Functioning Scales of the Functional Assessment of Cancer Therapy (FACT-Bl)

Baseline up to end of treatment (approximately 3 years)

Secondary

Overall Response Rate (ORR)

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.

Approximately up to 3 years

Secondary

Progression-free Survival (PFS)

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.

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)

Secondary

Change from Baseline in the Utility Scale of the EQ-5D-5L

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.

Baseline up to follow up phase (approximately 3 years)

Study 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

  -  Metastatic or surgically unresectable urothelial cancer

  -  Documented progression of disease, defined as any progression that requires a change
     in treatment, prior to randomization

  -  Cohort 1: Prior treatment with an anti-PD-(L) 1 agent as monotherapy or as combination
     therapy; no more than 2 prior lines of systemic treatment. Cohort 2: No prior
     treatment with an anti-PD-(L) 1 agent; only 1 line of prior systemic treatment.
     Subjects who received neoadjuvant or adjuvant chemotherapy and showed disease
     progression within 12 months of the last dose are considered to have received systemic
     therapy in the metastatic setting.

  -  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). The
     only allowed exceptions are: urothelial cancer, skin cancer treated within the last 24
     months that is considered completely cured, localized prostate cancer with a gleason
     score of 6 (treated within the last 24 months or untreated and under surveillance) and
     localized prostate cancer with a gleason score of 3+4 that has been treated more than
     6 months prior to full study screening and considered to have a very low risk of
     recurrence.

  -  Symptomatic central nervous system metastases

  -  Received prior fibroblast growth factor receptor (FGFR) inhibitor treatment

  -  Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients

  -  Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of
     any grade.

  -  History of uncontrolled cardiovascular disease

  -  Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers,
     known gastric ulcers, or unhealed incisions