NCT02722538已完成1 期
A Phase 1b, Multicenter, Open Label Study Evaluating Safety, Tolerability and Preliminary Efficacy of GemRIS 225 mg in Subjects With Muscle-Invasive Transitional Cell Carcinoma of the Bladder
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 6
- 主要终点
- Number of participants with treatment emergent adverse events (TEAEs) coded with MedDRA and graded for severity with CTCAE v4.0
研究概览
简要总结
The purpose of this study is to determine if TAR-200, an investigational drug-delivery system, is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) between diagnosis and radical cystectomy (RC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological proof of muscle-invasive transitional cell carcinoma of the bladder (stage II-III). Subjects with evidence of metastatic nodal disease to the obuturator or presacral lymph nodes only may be included (N1 M0). Subjects with any degree of fixation of the pelvic sidewall are not eligible.
- •In Arm 1, subjects must have residual visible tumor following TURBT. In Arm 2, subjects must be fully resected (i.e., no visible tumor or as little tumor as possible) after restaging TURBT 2-6 weeks prior to Study Day
- •Adequate bone marrow, liver, and renal function, as assessed by the following requirements conducted within 21 days prior to dosing:
- •Hemoglobin ≥ 9.0 g/dL
- •Absolute neutrophil count (ANC) ≥ 1,500/mm3
- •Platelet count ≥ 100,000/mm3
- •Total bilirubin ≤ 1.5xULN (upper limit of normal)
- •Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5xULN
- •Glomerular Filtration Rate (GFR) ≥ 30% (≥ 30 ml/min/1.73 m2)
- •Subjects must be willing to undergo a cystoscopy on study for investigational product removal.
- •Eligible for and willing to undergo RC per the attending urologist.
- •Subjects must be deemed ineligible for cisplatin-based combination chemotherapy by the attending medical oncologist.
- •Subjects medically eligible for neoadjuvant cisplatin-based combination chemotherapy who refuse this therapeutic option and understand the risks and benefits of doing so.
- •Prior radiation therapy is allowed provided that no radiation therapy was administered to the urinary bladder.
- •Written informed consent and Health Insurance Portability and Accountability Act of 1966 (HIPAA) authorization for release of personal health information.
- •Age > 18 years at the time of consent.
排除标准
- •Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome.
- •Prior systemic chemotherapy for transitional cell carcinoma of the bladder. Any other prior systemic chemotherapy for a non-urothelial carcinoma must have been completed > 5 years prior to initiation of study.
- •Previous exposure to gemcitabine instillations.
- •Currently receiving other intravesical chemotherapy.
- •Concurrent clinically significant infections as determined by the treating investigator.
- •Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use or removal of TAR-
- •Documented history of vesicoureteral reflux or the presence of an indwelling ureteral stent or nephrostomy tube at the time of screening.
- •Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥ 6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis.
- •Bladder Post-Void Residual Volume (PVR) of > 250-mL.
- •Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection that in the opinion of the investigator, contraindicates participation. Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study.
- •History or presence of any significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, gynecological, endocrine, immunological, dermatological, neurological or psychiatric disease or disorder that, in the opinion of the investigator, contraindicates participation.
- •History of diagnosis of neurogenic bladder.
- •Concomitant immunosuppressive medications, such as methotrexate or TNF inhibitors, within 2 weeks of Study Day 0, exclusive of steroid doses ≤ 5 mg daily.
- •Difficulty providing blood samples.
- •Unwilling or unable to provide informed consent or comply with the requirements of this protocol, including the presence of any condition (physical, mental or social) that is likely to affect the subject's return for scheduled visits and follow-up.
- •Other unspecified reasons that, in the opinion of the investigator or TARIS, make the subject unsuitable for enrollment.
研究组 & 干预措施
Residual Tumor following TURBT
Experimental
TAR-200 is placed into the bladder through an inserter on Study Day 0 and is removed on Study Day 7. TAR-200 releases gemcitabine gradually during the 7 day indwelling time. A second TAR-200 is placed in the bladder on Study Day 21 and is removed on Study Day 28, which is the day of the Radical Cystectomy (RC).
干预措施: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200 (Drug)
No Residual Tumor Following TURBT
Experimental
TAR-200 is placed into the bladder through an inserter on Study Day 0 and is removed on Study Day 7. TAR-200 releases gemcitabine gradually during the 7 day indwelling time. A second TAR-200 is placed in the bladder on Study Day 21 and is removed on Study Day 28, which is the day of the Radical Cystectomy (RC).
干预措施: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200 (Drug)
结局指标
主要结局
Number of participants with treatment emergent adverse events (TEAEs) coded with MedDRA and graded for severity with CTCAE v4.0
时间窗: Maximum 132 days
次要结局
- Tmax, plasma dFdU(From Day 0 up to Day 28)
- Cavg, plasma dFdU(From Day 0 up to Day 28)
- Tmax, plasma dFdC(From Day 0 up to Day 28)
- Cavg, urine dFdU (Arm 1 only)(From Day 0 up to Day 28)
- Tmax, urine dFdC (Arm 1 only)(From Day 0 up to Day 28)
- Cmax, plasma dFdU(From Day 0 up to Day 28)
- Cmax, plasma dFdC(From Day 0 up to Day 28)
- Cavg, plasma dFdC(From Day 0 up to Day 28)
- Cmax, urine dFdU (Arm 1 only)(From Day 0 up to Day 28)
- Tmax, urine dFdU (Arm 1 only)(From Day 0 up to Day 28)
- Cmax, urine dFdC (Arm 1 only)(From Day 0 up to Day 28)
- Number of participants who are tolerant of TAR-200 indwelling(From Day 21 up to Day 28)
- Percentage of participants who are tolerant of TAR-200 indwelling(From Day 21 up to Day 28)
- Cavg, urine dFdC (Arm 1 only)(From Day 0 up to Day 28)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (AKT) (Arm 1)(Anti-tumor analysis will occur at study visit Day 28.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD31) (Arm 2)(Anti-tumor analysis will occur at study visit Day 42.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD31) (Arm 1)(Anti-tumor analysis will occur at study visit Day 28.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD4) (Arm 1)(Anti-tumor analysis will occur at study visit Day 28.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (Ki67) (Arm 1)(Anti-tumor analysis will occur at study visit Day 28.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD8) (Arm 1)(Anti-tumor analysis will occur at study visit Day 28.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (TUNEL) (Arm 1)(Anti-tumor analysis will occur at study visit Day 28.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (PD-L1) (Arm 1)(Anti-tumor analysis will occur at study visit Day 28.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (AKT) (Arm 2)(Anti-tumor analysis will occur at study visit Day 42.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD4) (Arm 2)(Anti-tumor analysis will occur at study visit Day 42.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD8) (Arm 2)(Anti-tumor analysis will occur at study visit Day 42.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (PD-L1) (Arm 2)(Anti-tumor analysis will occur at study visit Day 42.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (Ki67) (Arm 2)(Anti-tumor analysis will occur at study visit Day 42.)
- Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (TUNEL) (Arm 2)(Anti-tumor analysis will occur at study visit Day 42.)
研究者
研究点 (6)
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