Neoadjuvent Dose-dense Gemcitabine and Cisplatin In Muscle Invasive Bladder Cancer

Официальное название

Neoadjuvent Dose-dense Gemcitabine and Cisplatin In Muscle Invasive Bladder Cancer:Results of a Phase 2 Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Gemcitabine and Cisplatin (DD GC)
  Participants will receive neoadjuvant ddGC, consisting of gemcitabine and cisplatin administered at shortened intervals (e.g., gemcitabine 1200 mg/m² on days 1 and 8, fractionated cisplatin 35 mg/m² on day 1and 8, every 14 days) with appropriate growth factor support. A total of four cycles are planned before radical cystectomy.

Первичные конечные точки

• Pathologic Complete Response (pT0N0) Rate [Срок оценки: At the time of radical cystectomy (approximately 4-6 weeks after completion of neoadjuvant chemotherapy).]

Критерии участия

Критерии включения

• Histologically confirmed urothelial carcinoma of the bladder, clinical stage T2-T4a, N0-N1, M0.
• Eligible and fit for cisplatin-based chemotherapy (e.g., creatinine clearance ≥ 60 mL/min).
• Candidate for radical cystectomy after neoadjuvant treatment.
• ECOG performance status 0-1.
• Adequate bone marrow, liver, and renal function as per institutional standards.

Критерии исключения

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 ≥ 2.
• Significant comorbidities contraindicating chemotherapy (e.g., uncontrolled cardiac disease, severe infection).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Египет · 1 центр

• Assiut university Hospital-Departement of clinical oncology. — Asyut

Идентификаторы

NCT: NCT07184021 · Early Urinary bladder cancer

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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