Safety and Efficacy of Neoadjuvant immunotherapy with Durvalumab (MEDI 4736) in combination with neoadjuvant chemotherapy (Gemcitabin/Cisplatin or Gemcitabin/Carboplatin) in patients with operable, high-risk, localized urothelial carcinoma of the upper urinary tract. iNDUCT - GETUG V08
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- In each cohort and independently the rate of patients who achieved a pathological complete response (PCR) after surgery will be assessed. Pathological complete response (PCR) is defined as no residual signs of viable tumor cells in tissue samples removed during surgery after treatment (yPT0). To find out if there is a pathologic complete response, a pathologist will perform an evaluation of the tissue samples under a microscope to see if there are still cancer cells left after the treatment.
研究概览
简要总结
To assess in each cohort and independently the pathological complete response (ypT0) rate of a combination therapy with neoadjuvant durvalumab and chemotherapy (Gemcitabine/Cisplatin or Carboplatin) before surgery in patients with high-risk, localized, non-metastatic urothelial carcinoma of the upper tract.
研究设计
- 分配方式
- Non-randomized
- 主要目的
- Controlled Single Arm Open-label Non-randomized
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •The patient has a histologically-confirmed (ureteroscopic biopsy) or cytologically(urine cytology)-confirmed diagnosis of high-grade urothelial carcinoma of the renal pelvis or ureter. Presence of divergent histologies (i.e. squamous-cell tumor, adenocarcinoma, small cell carcinoma, micropapillary variant) may be acceptable provided that there is an important prevalence (> 90%) of urothelial component.
- •Presence of either: o High-grade disease on ureteroscopic tumor biopsy OR o High-grade disease on urine cytology AND infiltrative aspect of renal pelvis/ureteral wall on CT imaging (presence of hydronephrosis will be considered invasive by definition) with negative cystoscopy. o In the absence of histological evidence, the opinion of the multidisciplinary consultation meeting (RCP) will prevail for the analysis of the imaging and the potential inclusion of the patient in the study
- •The patient is at least 18 years old. Patients older than 70 years will be evaluated for fragility with G8 score (Soubeyran et al. 2014). Patients with a G8 score of less than 14 will not be included in the study.
- •Body weight > 30 Kg.
- •No prior systemic therapies.
- •Patient must be eligible to radical nephroureterectomy surgery
- •ECOG performance status 0 to
- •M0 No or N1 disease on CT scan.
排除标准
- •Concomitant diagnosis of muscle invasive or in situ or high grade non muscle invasive urothelial carcinoma of the bladder.
- •Evidence of NYHA functional class III or IV heart disease.
- •Serious intercurrent medical or psychiatric illness, including serious active infection.
- •Concomitant use of any other investigational drugs.
- •Diagnosis of immunodeficiency or received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study registration.
- •Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
- •History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
结局指标
主要结局
In each cohort and independently the rate of patients who achieved a pathological complete response (PCR) after surgery will be assessed. Pathological complete response (PCR) is defined as no residual signs of viable tumor cells in tissue samples removed during surgery after treatment (yPT0). To find out if there is a pathologic complete response, a pathologist will perform an evaluation of the tissue samples under a microscope to see if there are still cancer cells left after the treatment.
In each cohort and independently the rate of patients who achieved a pathological complete response (PCR) after surgery will be assessed. Pathological complete response (PCR) is defined as no residual signs of viable tumor cells in tissue samples removed during surgery after treatment (yPT0). To find out if there is a pathologic complete response, a pathologist will perform an evaluation of the tissue samples under a microscope to see if there are still cancer cells left after the treatment.
次要结局
- In each cohort and independently: Rate of patients showing pathological partial response (PaR). PaR is defined as downstaging to neoadjuvant pathologic stage groups ≤ ypT1N0M0 (ypT0-Ta-Tis/T1 disease). The rate of patients with PaR will be calculated on the subpopulation of patients with ureteroscopic biopsy at diagnosis.
- In each cohort and independently: Assessment of safety and tolerability by analysing and interpreting Common Terminology Criteria for Adverse Event (CTCAE) until surgery using the National Cancer Institute, Division of Cancer Treatment and Diagnosis (DCTD) listing of CTCAE (NCI CTCAE V5.0).
- In each cohort and independently:The overall survival, bladder recurrence, dissemination will be collected at 2 years follow-up after surgery.
研究者
Pr Stéphane DROUPY
Scientific
Centre Hospitalier Universitaire De Nimes