Neoadjuvent Dose-dense Gemcitabine and Cisplatin In Muscle Invasive Bladder Cancer:Results of a Phase 2 Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Pathologic Complete Response (pT0N0) Rate
研究概览
简要总结
To evaluate the feasibility, safety, and pathological response of dose-dense neoadjuvant gemcitabine and cisplatin in patients with muscle-invasive bladder cancer, with the goal of improving tumor downstaging and optimizing outcomes before radical cystectomy.
详细描述
Muscle-invasive bladder cancer (MIBC) poses a significant therapeutic challenge due to its high risk of progression and metastasis. Radical cystectomy remains the cornerstone of curative treatment; however, many patients relapse due to undetected micrometastases at diagnosis. To address this, neoadjuvant chemotherapy (NAC) with cisplatin-based combinations has been established as standard care, demonstrating improved pathological downstaging and survival outcomes compared to surgery alone (Yin et al., 2020; Necchi et al., 2017).
Gemcitabine and cisplatin (GC) is widely favored in NAC because of its comparable efficacy to older regimens and a more favorable toxicity profile (Galsky et al., 2016). However, conventional schedules may be limited by treatment delays and incomplete cycles, often due to cumulative toxicities or patient frailty. Dose-dense chemotherapy-delivering the same drugs at shorter intervals with growth factor support-has been proposed to improve outcomes by intensifying dose intensity and reducing tumor repopulation between cycles (Zargar et al., 2018; Kulkarni et al., 2020).
Evaluating dose-dense GC in the neoadjuvant setting aims to balance efficacy and tolerability, potentially increasing rates of complete pathological response and improving long-term survival. This protocol seeks to explore the feasibility, safety, and oncological benefit of this approach in patients with MIBC.
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
- •Histologically confirmed urothelial carcinoma of the bladder, clinical stage T2-T4a, N0-N1, M
- •Eligible and fit for cisplatin-based chemotherapy (e.g., creatinine clearance ≥ 60 mL/min).
- •Candidate for radical cystectomy after neoadjuvant treatment.
- •ECOG performance status 0-
- •Adequate bone marrow, liver, and renal function as per institutional standards.
排除标准
- •Histology predominantly other than urothelial carcinoma (e.g., small cell, squamous cell ≥50%).
- •Clinical or radiological evidence of distant metastases (M1).
- •Prior systemic chemotherapy or radiotherapy for bladder cancer.
- •Significant renal impairm ent (creatinine clearance < 60 mL/min).
- •ECOG performance status ≥
- •Significant comorbidities contraindicating chemotherapy (e.g., uncontrolled cardiac disease, severe infection).
研究组 & 干预措施
Neoadjuvant Dose-Dense Gemcitabine and Cisplatin (DDGC)
Participants will receive four cycles of dose-dense gemcitabine and cisplatin (DDGC) prior to radical cystectomy. Each cycle consists of gemcitabine 1200 mg/m² intravenously on days 1 and 8, and fractionated cisplatin 35mg/m² intravenously on day 1and 8, repeated every 14 days. Pegfilgrastim 6 mg subcutaneously will be administered on day 2 of each cycle for growth factor support. Radical cystectomy will be performed 4-6 weeks after completion of chemotherapy.
干预措施: Gemcitabine and Cisplatin (DD GC) (Drug)
结局指标
主要结局
Pathologic Complete Response (pT0N0) Rate
时间窗: At the time of radical cystectomy (approximately 4-6 weeks after completion of neoadjuvant chemotherapy).
Proportion of participants with no residual invasive or non-invasive tumor in the bladder and no lymph node involvement (ypT0N0) at the time of radical cystectomy, as determined by histopathological examination of the surgical specimen.
次要结局
未报告次要终点
研究者
Nehal Ali Suliman
Assistant lecturer
Assiut University