NCT02138734招募中1 期
A Study of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With 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
- 招募中
- 入组人数
- 596
- 试验地点
- 141
- 主要终点
- Complete Response (CR) Rate
研究概览
简要总结
This is a Phase Ib/IIb, randomized, two-cohort, open-label, multicenter study of intravesical N-803 plus BCG versus BCG alone, in BCG naïve patients with high-grade NMIBC.
详细描述
The study includes a dose escalation phase (phase Ib) and an expansion phase (phase IIb).
In the phase Ib, patients will be treated with intravesical N-803 in combination with BCG. The purpose of the phase Ib portion of the study is to evaluate the safety, identify the Maximum Tolerated Dose (MTD) of N-803 and determine the Recommended Dose (RD) level of N-803 in combination with BCG for the phase IIb expansion.
In the phase IIb expansion, patients will be randomized to receive either intravesical N-803 in combination with BCG or BCG alone. Patients will be enrolled into one of two study cohorts (Cohort A and Cohort B). These will be two independent study cohorts, evaluated separately for treatment efficacy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell carcinoma high-grade subtype (mixed histology tumors allowed if transitional cell histology is predominant histology).
- •Cohort A: Histologically confirmed CIS (with or without Ta/T1 disease); Cohort B: Histologically confirmed high-grade papillary disease (Ta/T1 only).
- •Patients are eligible if the diagnostic biopsy was done within 3 months of treatment start and a cystoscopy demonstrating no resectable disease was done within 6 calendar weeks (inclusive of 48 days) of treatment start (residual CIS is acceptable; patients with T1 disease must undergo repeat resection if muscularis propria is not present in each biopsy sample). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment.
- •Upper tract imaging within 6 months prior to study entry must not be suspicious for upper tract malignancy.
- •Currently eligible for intravesical BCG therapy.
- •Age ≥ 18 years.
- •Performance status: ECOG performance status of 0, 1, or
- •BCG-naive disease as defined as either of the following:
- •Have not received prior intravesical BCG; or
- •Previously received BCG, but stopped receiving more than 3 years before date of randomization.
- •Laboratory tests performed within 21 days of treatment start:
- •Absolute lymphocyte count ≥ Institutional lower limit of normal
- •Absolute neutrophil count (AGC/ANC) ≥ 1,000/μL
- •Platelets ≥ 100,000/µL [Patients may be transfused to meet this requirement]
- •Hemoglobin ≥ 8 g/dL [Patients may be transfused to meet this requirement]
- •Calculated glomerular filtration rate (GFR*) >40 mL/min or Serum creatinine ≤ 1.5 x ULN
- •Total bilirubin ≤ 2.0 X ULN
- •AST, ALT, ALP ≤ 3.0 X ULN
- •Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction. PFT > 50% FEV1 if clinically indicated by the investigator.
- •Negative serum pregnancy test if female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized).
- •Female participants of childbearing potential must adhere to using a medically accepted method of birth control prior to screening and agree to continue its use during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use barrier methods of birth control while on study.
- •Provide signed informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations.
- •using the following Cockcroft-Gault equation to calculate the eGFR for this study: eGFR in mL/min = {(140-age in years) x (weight in kg) x F}/(serum creatinine in mg/dL x 72) Where F =1 if male; and 0.85 if female
排除标准
- •Prior BCG treatment or known hypersensitivity to BCG. Patients who have received more than a single-dose post-operative treatment of mitomycin-C or gemcitabine following the most recent screening TURBT/biopsy are excluded.
- •Concurrent use of other investigational agents (not including FDA-authorized drugs for the prevention and treatment of COVID-19).
- •History of or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer or any other cancer within the past 5 years, except: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage 1 or 2 cancer from which the patient is currently in complete remission, or stable prostate cancer (under active surveillance or hormone control).
- •Symptomatic congestive heart failure (CHF), NYHA (New York Heart Association) Class III or IV or other clinical signs of severe cardiac dysfunction.
- •Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry.
- •History or evidence of uncontrollable CNS disease.
- •Known HIV-positive.
- •Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
- •Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions.
- •Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily or equivalent).
- •Women who are pregnant or nursing. Female patients of childbearing potential must have a negative pregnancy test and must adhere to using a medically acceptable method of birth control prior to screening and agree to continue its use during the study and for 30 days after the last dose of study drug, or be surgically sterilized (e.g., hysterectomy or tubal ligation). Women of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Males must agree to use barrier methods of birth control while on study and for 90 days post last dose of study drug.
- •Psychiatric illness/social situations that would limit compliance with study requirements.
- •Other illness that in the opinion of the investigator would exclude the patient from participating in this study.
研究组 & 干预措施
N-803+BCG
Experimental
(Phase Ib and IIb) for BCG-naive patients
干预措施: BCG+N-803( 50mg BCG/ Instillation+ N-803( 400 μg/instillation). ) (Biological)
BCG alone
Active Comparator
(Phase IIb) for BCG-naive patients
干预措施: BCG( 50mg/Instillation) (Biological)
结局指标
主要结局
Complete Response (CR) Rate
时间窗: 6 Months
Patients in Cohort A: compare complete response rate between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology.
Disease Free Survival (DFS)
时间窗: 13 Years and 3 Months
Patients in Cohort B: compare disease-free survival between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology.
次要结局
- Progression-free survival (PFS)(13 Years and 3 Months)
- Overall survival(13 Years and 3 months)
- Disease specific survival(13 Years and 3 months)
- Time to disease worsening(13 Years and 3 Months)
- Cystectomy Free Rate(13 years and 3 months)
- Safety Profile: Number and severity of treatment emergent AEs [Time Frame: 39 Months](39 Months)
- Duration of Complete Response(13 Years and 3 months)
- Complete Response Rate( All Recurrent Bladder Cancer Including Low Grade Ta Disease)(13 Years and 3 months)
- Long Term Complete Response Rate(13 years and 3 Months)
- Duration of Complete Response ( All Recurrent Bladder Cancer Including Low Grade Ta Disease)(13 Years and 3 months)
- Cohort B: Disease Free Survival Rate(36 Months)
- Cohort B: Disease Free Survival(13 Years and 3 Months)
- Vital signs and clinical laboratory assessment(36 Months)
- Long Term Follow Up(LTFU) data from subjects who were treated(10 Years after treatment period visits)
研究者
研究点 (141)
Loading locations...
相似试验
尚未招募
2 期
Intravesical BCG in Combination With ALT-803 (N-803) in Patients With Non-Muscle Invasive Bladder Cancer.CTRI/2024/07/070765ImmunityBio Inc Altor BioScience
尚未招募
不适用
Analyzing the Urine During BCG Instillation in Bladder Cancer Patients for Disease FollowupBladder CancerNCT06153849Changhai Hospital100
尚未招募
不适用
Therapeutic effect of Intravesical Bacillus Calmette-Guerin(IMMUCYST) to nonmuscle-invasive urothelial carcinoma of bladder and examination of safetybladder cancerJPRN-UMIN000004672niversity of Kobe,Graduate school of medicine100
招募中
不适用
To study the effect of BCG vaccine in Reducing the Incidence and severity of COVID-19 in the high-risk populatioCTRI/2020/07/026668Indian Council of Medical Research
已完成
2 期
The Impact of Intravesical Gemcitabine and 1/3 Dose Bacillus Calmette-Guerin on the Quality of Life in Superficial Bladder CancerBladder CancerNCT01697306A.O.U. Città della Salute e della Scienza120