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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 150
- 主要终点
- Cohort 1: Recurrence-Free Survival (RFS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Erdafitinib (Drug)
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.
干预措施: Investigator Choice (Gemcitabine) (Drug)
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.
干预措施: Investigator Choice (Mitomycin C) (Drug)
Cohort 2
Participants with high-risk, BCG- unresponsive NMIBC presenting as CIS with or without concurrent papillary tumor will receive treatment with erdafitinib.
干预措施: Erdafitinib (Drug)
Cohort 3
Marker lesion study in intermediate-risk NMIBC presenting as papillary disease only. All enrolled participants will receive treatment with erdafitinib.
干预措施: Erdafitinib (Drug)
结局指标
主要结局
Cohort 1: Recurrence-Free Survival (RFS)
时间窗: From randomization (Cycle 1 Day 1, pre-dose) up to 48.2 months
RFS was defined as the time from the date of randomization until the date of the reappearance of high-risk disease (high-grade Ta, T1 or carcinoma in situ \[CIS\]), or death, whichever was reported first. Recurrence was assessed using cystoscopy, bladder mapping, urine cytology, and computed tomography (CT)/ magnetic resonance imaging (MRI) urogram. Participants who were recurrence-free and alive or had unknown status were censored at the last tumor assessment. The Kaplan-Meier method was used to estimate the distribution of overall RFS for each treatment group.
次要结局
- Plasma Concentrations of Erdafitinib(All cohorts: Pre-dose on Cycle 1 Day 14, pre-dose and 3 hours post-dose on Cycle 2 Day 1 (each cycle was of 28 days))
- Cohort 1: Recurrence-Free Survival Rate at 6 Months and 12 Months(At Month 6 and Month 12)
- Cohort 1: Overall Survival(From randomization (Cycle 1 Day 1, pre-dose) up to 48.2 months)
- Cohort 1: Time to Progression(From randomization (Cycle 1 Day 1, pre-dose) up to 48.2 months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From start of treatment (Day 1) up to 25.2 months)