Luminal Bladder Cancer Effective Response to Neoadjuvant Chemotherapy (LUMBER-NAC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- : Pathological upstaging rate at radical cystectomy (pT3-pT4 or pN+)
研究概览
简要总结
This study is a two-arm phase II randomized trial investigating patients with luminal subtype muscle-invasive bladder cancer (MIBC) receiving neoadjuvant therapy (NAT) followed by cystectomy compared to those receiving upfront cystectomy.
详细描述
The goal of this study is to assess the feasibility and oncologic safety of upfront radical cystectomy in luminal MIBC, using pathological upstaging (pT3-4 or pN+) and efficacy as the primary safety endpoints.
For patients with muscle-invasive bladder cancer (MIBC), the standard treatment remains sequential neoadjuvant therapy (NAT), which may include either cisplatin-based chemotherapy or novel approved combination regimens (i.e., chemotherapy and immunotherapy) followed by cystectomy. Although NAT improves overall survival, individual patient responses are heterogeneous (meaning not all patients experience the same benefit), and patients often experience morbidity.
In this study, the investigators will use the commercially available GSC- Decipher Bladder to analyze tumor tissue and determine the genomic subtype (luminal or basal).
Additionally, circulating tumor cell DNA (ctDNA) will be assessed at several time points in patients receiving NAT followed by RC, compared with those receiving upfront cystectomy.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •▪ Inclusion Criteria
- •Willing and able to provide informed consent
- •Age ≥18 years old
- •Eligible to receive standard of care systemic neoadjuvant therapy
- •Eastern Cooperative Group (ECOG) performance status of 0-1
- •Documented histologically confirmed urothelial muscle-invasive bladder cancer
- •cT2N0M0 bladder cancer based on pre-TURBT bimanual exam and cross-sectional imaging performed within 8 weeks of surgery or initiation of NAT.
- •Willing to undergo RC with urinary diversion
- •No signs of extravesical disease on pre-TURBT conventional imaging
- •Variant histology is allowed so long as the tumor is predominantly urothelial carcinoma.
- •No presence of LVI on TURBT
- •Decipher Bladder GSC test result
- •Ineligible for or refusing TMT
- •The population is adult men or women of any ethnicity diagnosed with muscle-invasive bladder cancer.
排除标准
- •Patients under 18 years old. Considering the minimal incidence of bladder cancer among the pediatric population, children are not eligible for this study.
- •Not willing or unable to give informed consent.
- •Clinical or pathological evidence of metastatic disease, including, non-regional lymph nodes, visceral lesions, and bone lesions.
- •Significant hepatic impairment (Serum bilirubin > 1.5x upper limit of normal).
- •Significant renal impairment (creatinine clearance <30 ml/min).
- •Predominant variant histology (i.e. nested, micropapillary, sarcomatoid, plasmacytoid, small cell)6
- •cT3 bladder cancer on pre-TURBT bimanual exam or with hydronephrosis on cross-sectional imaging performed within 8 weeks of surgery or initiation of NAT
- •TURBT specimen with lymphovascular invasion (LVI) cT4 or unresectable bladder cancer
- •Concurrent diagnoses of other, non-urothelial, malignancies or prior malignancy diagnoses within the past three years. Exceptions, determined at the discretion of the principal investigator, include squamous cell carcinoma, basal cell carcinoma, or other low-grade cancer not expected to progress or require surgical/systemic therapy.
- •Prior history of systemic treatment for non-urothelial malignancies in the past three years, including chemotherapy and immunotherapy.
- •Prior diagnosis or evidence of psychiatric or medical conditions that may prevent patients from giving full and properly informed consent.
- •Any medical, familial, psychiatric, or geographic considerations that may prevent patients from study participation or follow-up required by the study protocol
- •Patients (cN+) are excluded from participation and are not eligible for enrollment.
- •Prisoners, Individuals without Decisional Capacity, and Pregnant Women will be excluded.
研究组 & 干预措施
Neoadjuvant Systemic Therapy Followed by Radical Cystectomy
Participants receive standard-of-care neoadjuvant systemic therapy, as selected by the treating physician, followed by radical cystectomy with urinary diversion.
Interventions: Each specific drug regimen confirmed by the PI, plus Radical Cystectomy With Urinary Diversion.
干预措施: Neoadjuvant Therapy (Drug)
Neoadjuvant Systemic Therapy Followed by Radical Cystectomy
Participants receive standard-of-care neoadjuvant systemic therapy, as selected by the treating physician, followed by radical cystectomy with urinary diversion.
Interventions: Each specific drug regimen confirmed by the PI, plus Radical Cystectomy With Urinary Diversion.
干预措施: Upfront radical cystectomy (Procedure)
Upfront Radical Cystectomy
Participants proceed directly to radical cystectomy with urinary diversion without receiving initial neoadjuvant systemic therapy.
Intervention: Radical Cystectomy With Urinary Diversion
干预措施: Upfront radical cystectomy (Procedure)
结局指标
主要结局
: Pathological upstaging rate at radical cystectomy (pT3-pT4 or pN+)
时间窗: At the time of radical cystectomy
Percentage of evaluable participants in each study arm who are pathologically upstaged from clinical stage cT2N0 disease to pathological stage pT3-pT4 or pN+ disease, based on examination of the radical cystectomy specimen.
次要结局
- Change From Baseline in Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) Bladder Cancer Subscale (BlCS) Score(Baseline and 1, 3, and 6 months after radical cystectomy)
研究者
Saum Ghodoussipour
Director, Bladder and Urothelial Cancer Program, Rutgers Cancer Institute
Rutgers, The State University of New Jersey