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 |
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Recruitment Status :
Active, not recruiting
First Posted : November 21, 2019
Last Update Posted : March 27, 2024
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Sponsor:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Janssen Research & Development, LLC
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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 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 107 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 : | March 29, 2024 |
| Estimated Study Completion Date : | March 1, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Bladder cancer
MedlinePlus related topics:
Bladder Cancer
Drug Information
available for:
Erdafitinib
| Arm | Intervention/treatment |
|---|---|
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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.
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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 |
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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.
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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. |
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Experimental: Cohort 2
Participants with high-risk, BCG- unresponsive NMIBC presenting as CIS with or without concurrent papillary tumor will receive treatment with erdafitinib.
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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 |
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Experimental: Cohort 3
Marker lesion study in intermediate-risk NMIBC presenting as papillary disease only. All enrolled participants will receive treatment with erdafitinib.
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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 :
- 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 :
- 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.
- 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.
- Recurrence-Free Survival [ Time Frame: Months 6 and 12 ]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.
- 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.
- 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
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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-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
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
Locations
Show 150 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
| Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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 27, 2024 |
| Last Verified: | March 2024 |
| 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 |
| 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:
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Non muscle invasive bladder cancer (NMIBC) Bacillus calmette- guerin (BCG) failure BCG unresponsive |
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms Non-Muscle Invasive Bladder Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Urinary Bladder Diseases Urologic Diseases Male Urogenital Diseases Carcinoma |
Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Gemcitabine Mitomycins Mitomycin Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antibiotics, Antineoplastic Alkylating Agents Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors |