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)

Janssen (J&J Innovative Medicine)

Status and phase: Active, not recruiting; Phase 2

Conditions: Urinary Bladder Neoplasms

Treatments: Drug: Erdafitinib; Drug: Investigator Choice (Mitomycin C); Drug: Investigator Choice (Gemcitabine)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04172675

2023-510306-40-00 (Registry Identifier)

42756493BLC2003 (Other Identifier)

2019-002449-39 (EudraCT Number)

CR108699

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 107 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

107 participants in 4 patient groups

Cohort 1: Erdafitinib

Experimental group

Description:

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.

Treatment:

Drug: Erdafitinib

Cohort 1: Investigators Choice

Active Comparator group

Description:

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.

Treatment:

Drug: Investigator Choice (Gemcitabine)

Drug: Investigator Choice (Mitomycin C)

Cohort 2

Experimental group

Description:

Participants with high-risk, BCG- unresponsive NMIBC presenting as CIS with or without concurrent papillary tumor will receive treatment with erdafitinib.

Treatment:

Drug: Erdafitinib

Cohort 3

Experimental group

Description:

Marker lesion study in intermediate-risk NMIBC presenting as papillary disease only. All enrolled participants will receive treatment with erdafitinib.

Treatment:

Drug: Erdafitinib