The goal of this clinical trial is to learn whether a combination of two chemotherapy drugs, Gemcitabine and Docetaxel, can treat high-grade non-muscle-invasive bladder cancer (HG-NMIBC) in adults whose cancer failed conventional BCG therapy. The drugs are given directly into the bladder (intravesically), one immediately after the other. The study will also assess the safety of this treatment. The main questions it aims to answer are: Can this drug combination effectively treat HG-NMIBC that did not respond to BCG and help prevent the cancer from coming back, offering long-term protection? What side effects or medical issues do participants experience during treatment? Researchers will evaluate this non-surgical approach as a potential alternative to bladder removal surgery (radical cystectomy), with the goal of validating it as a bladder-sparing option in this setting. Participants will: * Go through a screening process, including tumor removal and imaging tests * Receive weekly bladder treatments with Gemcitabine followed by Docetaxel for 6 weeks * If the cancer responds, continue with similar once monthly treatments (maintenance therapy) for up to 2 years * Attend regular check-ups, including bladder exams, urine tests, biopsies, and optional quality-of-life surveys * Possibly receive a second 6-week treatment cycle if the cancer returns early * Be followed for up to 5 years to monitor long-term outcomes
The primary objective of this study is to evaluate the efficacy of intravesical sequential Gemcitabine and Docetaxel in patients with BCG-unresponsive, high-grade, non-muscle-invasive bladder cancer (HG-NMIBC). Efficacy will be measured by the complete response (CR) rate at approximately 3 months for patients with carcinoma in situ (CIS), and by the disease-free rate from high-grade disease at 3 months for patients with high-grade papillary Ta/T1 disease. CR will be confirmed through cystoscopy, urine cytology, and bladder biopsy. Disease-free rate in patients with high-grade papillary disease will be assessed by non-positive cytology and the absence of visible tumor (biopsy optional). Two distinct patient cohorts will be recruited for this trial: Arm A: Patients with CIS, either alone or with concurrent papillary tumors Arm B: Patients with high-grade papillary tumors (Ta and/or T1) without CIS Secondary objectives include characterizing the safety and toxicity profile of the treatment and evaluating additional efficacy outcomes such as high-grade recurrence-free survival (HGRFS), recurrence-free survival (RFS), progression-free survival (PFS), cystectomy-free survival (CFS), cancer-specific survival (CSS), overall survival (OS), and quality of life (QoL). The study will also assess outcomes in patients who experience early bladder cancer recurrence without progression and undergo a second 6-week induction cycle. This is a prospective, two-arm, multicenter cohort study conducted nationally and internationally. Participants will receive intravesical Gemcitabine immediately followed by Docetaxel once weekly for 6 weeks (induction phase), followed by similar once monthly treatments for up to 24 months (maintenance phase). Patients will be followed for up to 5 years to assess long-term outcomes.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
174
Sequential intravesical administration of Gemcitabine (1000mg) followed by Docetaxel (37 mg), delivered via sterile urethral catheter. Each drug is retained in the bladder for 60 minutes per instillation. The treatment consists of a 6-week induction phase (weekly instillations), followed by a 24-month maintenance phase (monthly instillations). This regimen is designed for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC), including carcinoma in situ (CIS) and high-grade papillary tumors (Ta/T1). The study evaluates efficacy, tolerability, and bladder preservation outcomes.
University of Iowa
Iowa City, Iowa, United States
Efficacy of Intravesical Gemcitabine/Docetaxel in BCG-Unresponsive Carcinoma In Situ NMIBC
To determine the efficacy of intravesical Gemcitabine/Docetaxel in patients with BCG-unresponsive carcinoma in situ (CIS) urothelial bladder carcinoma, as measured by the complete response (CR) rate (%) at approximately 3 months. CR will be determined through mandatory cystoscopy, urine cytology, and biopsy for those with CIS.
Time frame: 3 months
Efficacy of Intravesical Gemcitabine/Docetaxel in BCG-Unresponsive Papillary NMIBC
To determine the efficacy of intravesical Gemcitabine/Docetaxel in patients with BCG-unresponsive papillary urothelial bladder carcinoma, as measured by high-grade recurrence-free survival (HG RFS) rate (%) at approximately 3 months. Non-positive cytology and non-suspicious visual cystoscopic findings will determine lack of HG disease for subjects entering this study with papillary tumors (HG Ta T1).
Time frame: 3 months
Long-Term Efficacy of Intravesical Sequential Gemcitabine/Docetaxel in BCG-Unresponsive NMIBC
To assess duration of complete response for CIS +/- papillary TaT1 in month
Time frame: Up to 60 months (5 years) from initiation of treatment, with key evaluations at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, and 60 months
Long-Term Efficacy of Intravesical Sequential Gemcitabine/Docetaxel in BCG-Unresponsive NMIBC
To assess high-grade recurrence-free survival (HGRFS) for HG papillary only TaT1 in month
Time frame: Up to 60 months (5 years) from initiation of treatment, with key evaluations at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, and 60 months
Long-Term Efficacy of Intravesical Sequential Gemcitabine/Docetaxel in BCG-Unresponsive NMIBC
To assess recurrence-free survival (RFS) in month
Time frame: Up to 60 months (5 years) from initiation of treatment, with key evaluations at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, and 60 months
Long Term Efficacy of Intravesical Sequential Gemcitabine/Docetaxel in BCG-Unresponsive NMIBC
To assess progression-free survival (PFS) in month
Time frame: Up to 60 months (5 years) from initiation of treatment, with key evaluations at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, and 60 months
Long-Term Efficacy of Intravesical Sequential Gemcitabine/Docetaxel in BCG-Unresponsive NMIBC
To assess cystectomy-free survival (CFS) in month
Time frame: Up to 60 months (5 years) from initiation of treatment, with key evaluations at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, and 60 months
Long-Term Efficacy of Intravesical Sequential Gemcitabine/Docetaxel in BCG-Unresponsive NMIBC
To assess cancer-specific survival (CSS) in month
Time frame: Up to 60 months (5 years) from initiation of treatment, with key evaluations at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, and 60 months
Long-Term Efficacy of Intravesical Sequential Gemcitabine/Docetaxel in BCG-Unresponsive NMIBC
To assess overall survival in month
Time frame: Up to 60 months (5 years) from initiation of treatment, with key evaluations at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, and 60 months
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