A Phase 2, Two-arm Multicenter, Open-Label Study to Determine the Efficacy and the Safety of Two Different Dose Regimens of a pan-FGFR Tyrosine Kinase Inhibitor JNJ-42756493 in Subjects with Metastatic or Surgically Unresectable Urothelial Cancer with FGFR Genomic Alterations
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 22
- 试验地点
- 4
- 主要终点
- Plasma Concentration of Midazolam and its Metabolite (1-OH midazolam)
研究概览
简要总结
The purpose of this study is to evaluate the objective response rate (complete response [CR]+ partial response [PR]) of the selected dose regimen in participants with metastatic or surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations.
This is a multicenter, open-label study (participants will know the identity of study drugs administered) to evaluate the efficacy and safety of erdafitinib in participants with urothelial cancer. The study comprises a 30-days Screening Phase, a Treatment Phase comprised of 28-day treatment cycles that will continue until disease progression or unacceptable toxicity occurs, and a post treatment Follow-up Phase that will extend from the End of-Treatment Visit until the participant has died, withdraws consent, is lost to follow-up, or the end of the study, whichever comes first. The end of study is defined as the date when all participants have completed the study treatment (Regimens 1 to 3) or until the last participant enrolled under the drug-drug interaction (DDI) substudy completes the end of treatment visit,(whichever happens last). The purpose of DDI sub-study is to evaluate the interaction of repeated doses of erdafitinib with a sensitive cytochrome 450 (CYP) 3A substrate (midazolam) and with an organic cation transporter 2 (OCT2) probe substrate (metformin). Safety will be monitored throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Must have histologic demonstration of metastatic or surgically unresectable urothelial cancer. Minor components of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable.
- •Must have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline.
- •Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1, or
- •Must have adequate bone marrow, liver, and renal function as described in protocol.
- •Negative pregnancy test (urine or serum beta human chorionic gonadotropin [b-hCG]) at Screening for women of child bearing potential who are sexually active.
- •Must have shown disease progression according to RECIST, version 1.1, following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression according to RECIST, version 1.1, within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting. These participants will be referred to as chemo-refractory participants. (Participants who have shown disease progression according to RECIST, version 1.1 following prior treatment with anti-Programmed death-ligand 1 (anti PDL1/PD1) antibodies are also eligible) For DDI substudy.
- •Disease progression following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting.
排除标准
- •Received chemotherapy, targeted therapies, definitive radiotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and mitomycin C, within 6 weeks; in the case of immunotherapy, within 4 weeks) before the first administration of study drug. Localized palliative radiation therapy (but should not include radiation to target lesions) and ongoing bisphosphonates and denosumab, are permitted.
- •Has persistent phosphate level greater than upper limit of normal (ULN) during screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical management.
- •Has a history of or current uncontrolled cardiovascular disease.
- •Females who are pregnant, breast-feeding, or planning to become pregnant within 3 months after the last dose of study drug and males who plan to father a child while enrolled in this study or within 5 months after the last dose of study drug.
- •Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, or Grade 1 neuropathy).
结局指标
主要结局
Plasma Concentration of Midazolam and its Metabolite (1-OH midazolam)
时间窗: Plasma Concentration of Midazolam and its Metabolite (1-OH midazolam) at Day-2 and Day 15
次要结局
未报告次要终点