Neoadjuvent Dose-dense Gemcitabine and Cisplatin In Muscle Invasive Bladder Cancer (No Acronym)

Assiut University

Status and phase: Not yet enrolling; Phase 2

Conditions: Urinary Bladder Cancer

Treatments: Drug: Gemcitabine and Cisplatin (DD GC)

Study type: Interventional

Funder types: Other

Identifiers

NCT07184021

Early Urinary bladder cancer

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Neoadjuvant Dose-Dense Gemcitabine and Cisplatin (DDGC)

Experimental group

Description:

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.

Treatment:

Drug: Gemcitabine and Cisplatin (DD GC)