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Trial record 1 of 1 for:    Janssen BLC2003 | Bladder Cancer
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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)

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ClinicalTrials.gov Identifier: NCT04172675
Recruitment Status : Recruiting
First Posted : November 21, 2019
Last Update Posted : March 30, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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.

Condition or disease Intervention/treatment Phase
Urinary Bladder Neoplasms Drug: Erdafitinib Drug: Investigator Choice (Gemcitabine) Drug: Investigator Choice (Mitomycin C) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 28, 2020
Estimated Primary Completion Date : October 26, 2022
Estimated Study Completion Date : May 11, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
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 Name: 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)/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.
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 Name: 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 Name: JNJ-42756493




Primary Outcome Measures :
  1. Recurrence-Free Survival (RFS) [ Time Frame: Up to 4 years ]
    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 :
  1. Time to Progression [ Time Frame: Up to 4 years ]
    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.

  2. Time to Disease Worsening [ Time Frame: Up to 4 years ]
    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.

  3. Disease-Specific Survival [ Time Frame: Up to 4 years ]
    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.

  4. Overall Survival [ Time Frame: Up to 4 years ]
    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.

  5. Recurrence-Free Survival [ Time Frame: Months 6, 12, and 24 ]
    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.

  6. Recurrence-Free Survival 2 (RFS2) [ Time Frame: Up to 4 years ]
    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.

  7. RFS by Central Histopathologic Review [ Time Frame: Up to 4 years ]
    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.

  8. Plasma Concentration of Erdafitinib [ Time Frame: Cycle 1 Day 14, Cycle 2 Day 1 (each cycle is of 28 days) ]
    Plasma concentration of erdafitinib will be reported.

  9. Number of Participants with Adverse events [ Time Frame: Up to 4 years ]
    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

  10. Change from Baseline in Patient's Global Impression of Severity (of cancer) (PGIS) [ Time Frame: Baseline up to 4 years ]
    PGIS is single-item questionnaires to evaluate patient's global impression of severity.

  11. 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) ]
    PGIC is single-item questionnaires to evaluate a patient's global impression of change of cancer.

  12. 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 ]
    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.

  13. Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 [ Time Frame: Baseline up to 4 years ]
    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.

  14. Change from Baseline in EuroQol European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) [ Time Frame: Baseline up to 4 years ]
    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.

  15. 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) ]
    Cmax is the maximum observed analyte concentration.

  16. 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) ]
    Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

  17. 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) ]
    AUClast defined as time zero to the time of the last measurable (non-below quantification limit [BQL]) analyte concentration.

  18. 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) ]
    AUCinfinity is defined as time zero to infinite time.

  19. Maximum Observed Plasma Concentration (Cmax) of Metformin [ Time Frame: Predose, Cycle 1 Day 14 (each cycle is of 28 days) ]
    Cmax is the maximum observed analyte concentration.

  20. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin [ Time Frame: Predose, Cycle 1 Day 14 (each cycle is of 28 days) ]
    Tmax is defined as actual sampling time to reach maximum observed plasma concentration.

  21. 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) ]
    AUClast defined as time zero to the time of the last measurable (non-below quantification limit [BQL]) analyte concentration

  22. 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) ]
    AUCinfinity is defined as time zero to infinite time.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04172675


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Additional Information:
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04172675    
Other Study ID Numbers: CR108699
2019-002449-39 ( EudraCT Number )
42756493BLC2003 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: November 21, 2019    Key Record Dates
Last Update Posted: March 30, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Janssen Research & Development, LLC:
Non muscle invasive bladder cancer (NMIBC)
Bacillus calmette- guerin (BCG) failure
BCG unresponsive
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Gemcitabine
Mitomycins
Mitomycin
BCG Vaccine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Alkylating Agents
Nucleic Acid Synthesis Inhibitors
Adjuvants, Immunologic