Comparison of drug combination (gemcitabine and docetaxel) with BCG to determine better cancer survival and patient specific results for use after transurethral endoscopic surgery in non-invasive urinary bladder mass

Not yet recruiting

Conditions: Other specified disorders of bladder,

Registration Number: CTRI/2025/04/084434

Lead Sponsor: Aviral Srivastava

Brief Summary: Carcinoma urinary bladder is a significant global health concern, accounting for approximately 3% of all cancer diagnosed worldwide and 2.1% of all cancer deaths [1]. Accurate staging and risk stratification aim to assess likelihood of tumour recurrence and progression and are crucial for determining appropriate treatment approaches in urothelial bladder carcinoma. Non-muscle invasive bladder cancer (NMIBC) comprises about 70% of all newly diagnosed bladder cancer cases [4]. It includes tumours with stage Ta, T1, and carcinoma in situ (CIS) [4]. NMIBC classified into low, intermediate, and high-risk groups based on factors such as tumour grade, stage, tumour number and size, presence of concurrent carcinoma in situ (CIS), age, gender, lymphovascular invasion, depth of lamina propria invasion and prior recurrence rate [4]. The European Organization for Research and Treatment of Cancer (EORTC) risk tables are established predictive models for recurrence and progression risk assessment in NMIBC [5].

Treatment decisions are typically made in a multidisciplinary setting, considering the available evidence, guidelines, and individual patient factors. Adjuvant therapy is given after initial surgery to reduce risk of disease recurrence and progression. Intravesical instillation of live attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) immunotherapy is the standard adjuvant treatment for treatment for non-muscle invasive bladder cancer (NMIBC) [6]. BCG stimulates innate and adaptive immune system to mount a localized immune response (macrophages, dendritic cells, cytokines, T-lymphocytes, natural killer cells, and other immune effector cells) against bladder cancer cells, thereby reducing tumour burden and preventing disease recurrence [7]. BCG immunotherapy is associated with potential local bladder-related adverse effects - malaise, dysuria, haematuria, BCG sepsis, granulomatous prostatitis- and treatment failure (30-40% of patients) [7]. Factors associated with treatment failure include high-grade tumours, presence of carcinoma in situ (CIS), and variant histology [7].

Intravesical chemotherapy agents, such as gemcitabine, docetaxel or mitomycin C, are alternatives under evaluation being used alone or in combination with BCG in specific cases. Gemcitabine is a nucleoside analogue that primarily affects the S-phase, inhibiting DNA synthesis by incorporating into replicating DNA strands, leading to chain termination and inducing apoptosis, while enhancing antitumor immune response [8]. Docetaxel (taxanes) acts by stabilizing microtubules and preventing depolymerization during cell division which disrupts mitosis and leads to cell cycle arrest, apoptosis, and inhibition of tumour cell growth [9]. The combination of gemcitabine and docetaxel theoretically provides a synergistic effect, with both drugs targeting different aspects of cell division and DNA synthesis, leading to enhanced antitumor activity. Combination of gemcitabine and docetaxel has demonstrated synergistic effects and enhanced antitumor activity in preclinical and clinical studies compared to single-agent chemotherapy [10]. Gemcitabine and docetaxel combination therapy can cause adverse effects viz. myelosuppression, fatigue, neuropathy, nausea, and hair loss. However, specific safety profile in the adjuvant setting for urothelial carcinoma of the bladder is not well-established and requires further investigation through clinical trials.

Assessing the impact on quality of life and patient-reported outcomes is crucial when comparing different treatment options. Studies evaluating the quality of life and patient-reported outcomes for gemcitabine and docetaxel combination therapy versus BCG in the adjuvant setting are limited [11]. Hence this study is being carried out to determine Recurrence-free survival (RFS) and Progression-free survival (PFS) of BCG-naive intermediate/ high grade non-muscle invasive bladder cancer patients treated with intravesical BCG vs Gemcitabine + Docetaxel, and to compare safety/toxicity and efficacy, overall survival (OS) and QOL (Quality of Life) in BCG-naive intermediate/ high grade non-muscle invasive bladder cancer patients treated with intravesical BCG vs Gemcitabine + Docetaxel

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Yet Recruiting

Sex: All

Target Recruitment: 80

Inclusion Criteria

1.Age: 18 to 80 years.
2.ECOG performance status 0-2 3.Complete clearance achieved during TURBT 4.Post TURBT- intermediate and high-risk NMIBC (as per EAU risk group) 5.Patients of either gender 6.Willingness to participate in study.

Exclusion Criteria

Histopathological diagnosis of MIBC/ non cancer 2.
Patients with concomitant upper tract urothelial cancer 3.
Known hypersensitivity/prior systematic therapy-Gemcitabine, Docetaxel or BCG 4.
Prior recipients of intravesical therapy for NMIBC within 6 months 5.
Hepatic or Renal dysfunction/ Pregnancy 6.
Active UTI/ GUTB 7.
Patients who refuse to give consent 8.
Variant histology (squamous cell carcinoma / adenocarcinoma / neuroendocrine carcinoma/ sarcomatoid, micropapillary, or plasmacytoid).

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Recurrence free survival and progression free survival	1 year

Secondary Outcome Measures

Name	Time	Method
adverse effects and cost-benefit	1 year

Trial Locations

Locations (1): Insititue of Medical Sciences, Banaras Hindu University
🇮🇳
Varanasi, UTTAR PRADESH, India
Insititue of Medical Sciences, Banaras Hindu University
🇮🇳Varanasi, UTTAR PRADESH, India
AVIRAL SRIVASTAVA
Principal investigator
7727093436
aviralsri7@gmail.com