Phase 2 Window of Opportunity Study of Pemigatinib in Non-muscle Invasive Bladder Cancer Patients With Recurrent Low- or Intermediate-Risk Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 6
- 主要终点
- Complete response rate of pemigatinib therapy
研究概览
简要总结
This phase II trial studies how well Pemigatinib (an orally administered inhibitor of fibroblast growth factor receptors 1, 2, and 3) works in non-muscle invasive bladder cancer (NMIBC) patients with recurrent tumors and a prior history of low- or intermediate-risk NMIBC tumors. Participants will receive pemigatinib for 4-6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT).
详细描述
It is a single-arm phase 2 window of opportunity study to assess the antineoplastic activity of pemigatinib in non-muscle invasive bladder cancer (NMIBC) patients with recurrent tumors and a prior history of low- or intermediate-risk NMIBC tumors. Enrolled patients will receive pemigatinib for 4-6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT). The primary endpoint will be complete response rate as determined at TURBT. Secondary endpoints will include safety profile, associations between complete response rate and tumor mutation/fusion status (e.g. FGFR3 specifically, others will also be examined) and NMIBC risk group (low- vs. intermediate-risk), and assessment of pemigatinib post-treatment urothelial tissue concentrations. The study will be conducted at 4-5 high volume bladder cancer institutions within the US and managed through the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center clinical research office.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Prior histologically confirmed low- or intermediate-risk non-muscle invasive urothelial carcinoma of the bladder (NMIBC) defined according to the following characteristics:
- •Initial tumor with all of the following:
- •Solitary tumor
- •Low-grade
- •Intermediate Risk
- •--- All tumors not defined in the two adjacent categories (between the category of low- and high-risk)
- •High Risk
- •High-grade
- •Multiple and recurrent and large (>3 cm) Ta low-grade tumors (all conditions must be met for this point on Ta low-grade tumors)
- •Documented tumor recurrence as noted in standard of care follow up cystoscopy.
- •ECOG (WHO) performance status 0-2
- •Age ≥ 18 years old
- •Patients must have the following laboratory values:
- •White blood cell count (WBC) > 3.0 K/mm3
- •Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
- •Platelets ≥ 100 K/mm3
- •Hemoglobin (Hgb) ≥ 9 g/dL
- •Serum total bilirubin: ≤ 1.5 x ULN
- •ALT and AST ≤ 3.0 x ULN
- •Serum calcium < ULN
- •Serum phosphate < ULN
- •Serum creatinine ≤ 1.5 x ULN or serum creatinine > 1.5 - 3 x ULN if calculated creatinine clearance (CrCl) is ≥ 30 mL/min using the modified Cockcroft-Gault equation
- •Patients who give a written informed consent obtained according to local guidelines
排除标准
- •Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma.
- •Patients with high grade urothelial carcinoma on their most recent urine cytology.
- •Patients with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer. (Patients that have completed all necessary therapy and are considered to be at less than 30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment.)
- •Patients who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
- •Patients who have received prior selective fibroblast growth factor receptor targeting agents (i.e. pemigatinib, dovitinib, BGJ398, AZD4547, JNJ-42756493, etc.).
- •Patients who have had radiotherapy ≤ 4 weeks prior to starting study drug, or who have not recovered from radiotherapy toxicities
- •Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
研究组 & 干预措施
Treatment: Pemigatinib
Patients will receive pemigatinib for 4 to 6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT).
干预措施: Pemigatinib (Drug)
结局指标
主要结局
Complete response rate of pemigatinib therapy
时间窗: 6 weeks
The number of participants with a complete response to pemigatinib therapy. Tumor complete response is defined as the complete absence of any stage bladder tumor on post-treatment Transurethral Resection of a Bladder Tumor (TURBT) and no evidence of recurrent urothelial carcinoma on post-treatment urine cytology.
次要结局
- Characterize the safety profile of pemigatinib therapy(4 years)
- Number of Participants with Complete Response and FGFR3 Mutational Status(Up to 4 weeks)
- Maximal concentration (Cmax, nmol/L) of pemigatinib in urothelial tissue at post-treatment TURBT(Up to 4 weeks)
- Relapse Free Survival (RFS) at 6 months(6 months)
- Relapse Free Survival (RFS) at 12 months(12 months)
- Number of Participants with Non-Muscle Invasive Bladder Cancer (NMIBC) and Complete Response(Up to 4 years)
- Relapse Free Survival (RFS) at 24 months(24 months)