Intravesical Gemcitabine and Docetaxel for High-Risk, BCG-Unresponsive Non-Muscle Invasive Bladder Cancer: A Prospective Cohort Study (GEMDOCE-BU)
概览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Michael A. O'Donnell
- 入组人数
- 174
- 试验地点
- 1
- 主要终点
- Efficacy of Intravesical Gemcitabine/Docetaxel in BCG-Unresponsive Carcinoma In Situ NMIBC
概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of urothelial carcinoma of the bladder without synchronous or metachronous upper tract involvement or prostatic urethral involvement. Subjects with negative upper tract imaging within 6 months of the study start and visually normal prostates are potentially eligible. Those with a history of suspicious upper tract cytology or suspicious prostatic urethra visually will require additional upper tract washes and/or biopsies to rule out concurrent extravesical disease.
- •Eligible bladder cancer presentations include:
- •Carcinoma in situ (CIS), with or without non-muscle-invasive stage Ta or T1 tumors of any grade.
- •High-Grade Papillary tumors (stages Ta and/or T1) without CIS.
- •All visible bladder tumors must be completely resected within 8 weeks prior to initiating intravesical Gem/Doce therapy.
- •If more than 8 weeks have passed since diagnosis or resection of index bladder CIS ± non-invasive tumor (pTa or T1 tumors), an office cystoscopy must be performed within 8 weeks of Gem/Doce initiation to confirm no visible tumor regrowth.
- •BCG-Unresponsive Disease as defined by any of the following FDA-accepted criteria:
- •Occurrence of high-grade, stage T1 cancer after at least 5/6 weekly BCG induction treatments.
- •Occurrence of CIS within 12 months, or high-grade papillary disease, stage Ta/T1, within 6 months after an "adequate" course of BCG therapy.
- •An "adequate" course of BCG includes at least 5/6 weekly BCG induction treatments and at least 2/3 weekly BCG maintenance or 2/6 weekly BCG re-induction treatments.
排除标准
- •History or concurrent Stage T2 or greater urothelial cancer.
- •History or concurrent upper tract or prostatic urethral cancer (no suspicious or positive upper tract cytology and negative upper tract imaging within 6 months of study entry; visually normal or absent prostatic urethra by cystoscopy).
- •History or concurrent variant bladder cancer histology including squamous cell carcinoma, adenocarcinoma, small cell carcinoma, plasmacytoid carcinoma, nested urothelial carcinoma, sarcomatoid carcinoma, squamous, glandular, metastatic carcinoma and others. Select urothelial carcinoma with favorable micropapillary differentiation is permitted (see above).
- •Active other malignancies excluding indolent or well-controlled prostate cancer, basal or squamous cell skin cancers or non-invasive cancer of the cervix are permitted so long as they are not expected to impact 3-year survival outcomes.
- •History of severe hypersensitivity reaction (\>= grade 3) to Gemcitabine and/or Docetaxel.
- •History of severe hypersensitivity reaction (\>= grade 3) to Polysorbate 80 containing drugs (Docetaxel is formulated with Polysorbate 80)
- •Concurrent treatment with any intravesical or systemic chemotherapeutic agent (8-week washout required).
- •Treatment with a checkpoint inhibitor within 2 treatment cycles of enrollment.
- •Major surgery within 3 months of enrollment.
- •Inadequate organ and bone marrow function as evidenced by:
研究组 & 干预措施
Arm A
High-grade non-muscle-invasive bladder cancer (HG NMIBC) with carcinoma in situ (CIS), either as pure CIS or concurrent with papillary tumors.
干预措施: Intravesical Gemcitabine and Docetaxel (Drug)
Arm B
High-grade non-muscle-invasive bladder cancer (HG NMIBC) with high-grade papillary tumors (stages Ta and/or T1) without carcinoma in situ (CIS).
干预措施: Intravesical Gemcitabine and Docetaxel (Drug)
结局指标
主要结局
Efficacy of Intravesical Gemcitabine/Docetaxel in BCG-Unresponsive Carcinoma In Situ NMIBC
时间窗: 3 months
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.
Efficacy of Intravesical Gemcitabine/Docetaxel in BCG-Unresponsive Papillary NMIBC
时间窗: 3 months
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).
次要结局
- Long Term Efficacy of Intravesical Sequential Gemcitabine/Docetaxel in BCG-Unresponsive NMIBC(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(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)
研究者
Michael A. O'Donnell
Professor
University of Iowa