NCT04089163撤回1 期
Toca 8: A Multicenter, Open-Label, Phase 1 Study to Evaluate the Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Recurrent High Grade Non-Muscle Invasive Bladder Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Tocagen Inc.
- 主要终点
- Dose-limiting toxicities
研究概览
简要总结
This is a Phase 1, multicenter, open-label study of intravesical Toca 511 followed by oral Toca FC in patients with high grade (HG) non-muscle invasive bladder cancer (NMIBC), with cohort expansion at the recommended Phase 2 dose. Patients with recurrent HG NMIBC who are undergoing planned transurethral resection of bladder tumor (TURBT) will be enrolled into the study, subject to meeting all entry criteria.
研究设计
- 研究类型
- Interventional
- 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
- •Provide written informed consent to participate
- •At least 18 years of age
- •Recurrent HG NMIBC, with HG tumor on previous histopathology
- •Undergoing planned TURBT and biopsy of CIS suspicious areas
- •No imaging findings consistent with T2 or greater disease, hydronephrosis, extravesical disease, nodal involvement, metastases, or other malignancies.
- •Able and willing to wait at least 2 weeks following intravesical administration of Toca 511 to undergo TURBT
- •If patient is a candidate for standard of care (SOC) intravesical therapy, able and willing to wait at least 2 weeks post-TURBT for initiation of such treatment
- •Patient is able to be catheterized and is anticipated to be able to retain Toca 511 for approximately 2 hours
- •Estimated life expectancy of at least 12 months
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •Patient has adequate organ function, as indicated by the following laboratory values
- •Complete blood count: hemoglobin ≥ 10 g/dL, platelet count ≥ 100,000/mm^3, absolute neutrophil count ≥ 1,500/ mm^3, absolute lymphocyte count ≥ 500/ mm^3
- •Liver: total bilirubin ≤ 1.5 × the upper limit of normal (ULN; unless known Gilbert's syndrome); alanine aminotransferase ≤ 2.5 × ULN
- •Kidney: estimated glomerular filtration rate (GFR: Cockcroft-Gault) ≥ 50 mL/min
- •Women of childbearing potential (defined as not postmenopausal [ie, ≥ 12 months of non-therapy-induced amenorrhea] or not surgically sterile) must have a negative serum pregnancy test within 7 days prior to administration of Toca 511, and be willing to use an effective means of contraception in addition to barrier methods (condoms) for the duration of the study.
- •Patient and partner are willing to use condoms for 12 months after receiving Toca 511 and/or 30 days after the last dose of Toca FC, and/or until there is no evidence of the virus in his/her blood or urine, whichever is longer.
排除标准
- •History of urothelial cancer in the upper tract or urethra; muscle invasive bladder cancer; or metastatic bladder cancer
- •History of bladder tumors other than urothelial carcinoma (ie, neuroendocrine, adenocarcinoma, or squamous cell carcinoma)
- •Treatment with intravesical agents within 28 days prior to Toca 511 administration
- •TURBT within 12 weeks prior to planned Toca 511 administration
- •History of pelvic radiation
- •Bladder tumor located within a bladder diverticulum
- •Genitourinary procedures (eg, prostate surgery; treatment of ureteral stones or moderate to extensive urethral stricture disease) prior to, during, or planned within the 4 weeks following TURBT, other than procedures for treatment of bladder tumors
- •Severe lower urinary tract dysfunction clinically manifest as poor capacity, disabling incontinence, chronic catheter use, or chronic infections or stones
- •Presence of suprapubic catheter
- •History of other malignancy, unless the patient has been disease-free for at least 5 years. Adequately treated basal cell carcinoma or squamous cell skin cancer is acceptable regardless of time, as well as cervical carcinoma in situ or localized prostate carcinoma, after curative treatment. (Note: Men with very low or low risk prostate cancer on active surveillance are acceptable candidates for this study.)
- •Active infection requiring antibiotic, antifungal, or antiviral therapy within 2 weeks prior to administration of Toca 511
- •Investigational treatment within 2 weeks or immunotherapy or antibody therapy within 28 days prior to Toca 511 administration, and/or has not recovered from toxicities associated with such treatment
- •Chronic treatment with autoimmune medications
- •Human immunodeficiency virus (HIV) seropositive
- •Pregnant or breast feeding
- •Bleeding diathesis, or required to take anticoagulants or antiplatelet agents, including nonsteroidal anti-inflammatory drugs, that cannot be stopped for surgery
- •Severe pulmonary, cardiac, or other systemic disease, specifically:
- •New York Heart Association > Class II congestive heart failure that is not controlled on standard therapy within 6 months prior to Toca 511 administration
- •Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes), clinically significant pulmonary disease (such as ≥ Grade 2 dyspnea)
- •Any other serious medical, social, or psychological condition that, based on Investigator assessment, may affect the patient's compliance or place the patient at an increased risk of potential treatment complications
- •History of allergy or intolerance to flucytosine
- •Presence of a condition that would prevent the patient from being able to swallow Toca FC tablets
研究组 & 干预措施
Sequential Dose Cohorts
Experimental
Doses of Toca 511 will be evaluated in sequential cohorts. Toca 511 will be administered as a single intravesical instillation. Following Toca 511 administration, Toca FC will be administered orally at a dose of 220 mg/kg/day for 7 days every 6 weeks.
干预措施: Toca 511 (Biological)
Sequential Dose Cohorts
Experimental
Doses of Toca 511 will be evaluated in sequential cohorts. Toca 511 will be administered as a single intravesical instillation. Following Toca 511 administration, Toca FC will be administered orally at a dose of 220 mg/kg/day for 7 days every 6 weeks.
干预措施: Toca FC (extended-release formulation of flucytosine) (Drug)
结局指标
主要结局
Dose-limiting toxicities
时间窗: 5 weeks
* Any treatment-related Grade 3 or higher non-hematologic toxicity, excluding nausea, vomiting, or diarrhea that are controllable with appropriate medical measures (eg, antiemetics, antimotility drugs) * Any treatment-related Grade 4 or higher hematologic toxicity
次要结局
- Differences in viral transduction of Toca 511 at each dose level, based on quantitation of viral RNA and DNA in tumor(3 weeks (+/- 1 week))
- Clearance of viral RNA in plasma and urine, based on real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and of viral DNA in whole blood and urine, based on quantitative PCR (qPCR)(1 week for plasma, 4 weeks for urine)
研究者
相似试验
已完成
3 期
Efficacy and Safety of Turoctocog Alfa Pegol (N8-GP) for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Chinese Patients With Haemophilia A (pathfinder10)Haemophilia ANCT05082116Novo Nordisk A/S36
已完成
2 期
A Randomised phase II multi-centre Trial of topical treatment in women with Vulval Intraepithelial NeoplasiaVulval Intraepithelial NeoplasiaCancerISRCTN34420460Cardiff University (UK)180
进行中（未招募）
1 期
Study to Evaluate the Efficacy, Safety and Pharmacokinetics of CT041 Autologous CAR T-cell InjectionGastric AdenocarcinomaGastroesophageal Junction AdenocarcinomaPancreatic CancerNCT04581473CARsgen Therapeutics Co., Ltd.192
已完成
1 期
Phase Ib/II Study of Sulfatinib in Treating Advanced Neuroendocrine TumorsNeuroendocrine TumorsNCT02267967Hutchison Medipharma Limited81
招募中
1 期
Evaluate the Safety, Tolerability, Pharmacokinetic Profile, Efficacy of Bl-M11D1Relapsed/Refractory Acute Myeloid LeukemiaNCT06714591SystImmune Inc.120