A Randomized Trial of Bicalutamide in Non-Muscle Invasive Bladder Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 6
- 主要终点
- Average Epidermal Growth Factor Receptor (EGFR) expression level
研究概览
简要总结
This phase I trial evaluates the effects of bicalutamide, compared to no study drug (NSD), on epidermal growth factor receptor (EGFR) protein expression in patients with non-muscle invasive bladder cancer. Bicalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Previous studies have suggested that expression of a protein called EGFR on tumor cells is related to bladder cancer disease progression. This trial may help doctors evaluate if bicalutamide has any effect on EGFR expression in patients with non-muscle invasive bladder cancer.
详细描述
PRIMARY OBJECTIVE:
I. To compare epidermal growth factor receptor (EGFR) messenger ribonucleic acid (mRNA) expression measured by reverse transcriptase polymerase chain reaction (rt-PCR) in normal appearing urothelium adjacent to tumor (measured as a ratio relative to urothelium and lamina-propria specific markers) in participants treated with anti-androgen therapy versus (vs.) participants given NSD.
SECONDARY OBJECTIVES:
I. To determine effect of bicalutamide on EGFR expression (by rtPCR) in the subgroup of patients whose normal appearing urothelium adjacent to tumor expresses the androgen receptor (AR) (at least "1" by immunohistochemistry [IHC] score).
II. To correlate AR expression in adjacent urothelium (by IHC score) with EGFR expression by rtPCR in participants randomized to bicalutamide versus NSD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The participants and the study team will be blinded.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Biologic male adults (>= 18 years old)
- •Note: Because no dosing or adverse event (AE) data are currently available on the use of bicalutamide in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable
- •Have suspected non-muscle invasive bladder carcinoma (NMIBC) on clinic-based cystoscopy or imaging as viewed by an American Urological Association (AUA) board-certified urologist
- •Have had cross sectional imaging of the abdomen and pelvis (computed tomography [CT] or magnetic resonance imaging [MRI] with or without contrast) within 6 months prior to enrollment with no signs of upper tract urothelial cancer (UC), invasive, nor metastatic disease
- •Note: If adenopathy or upper tract abnormalities are identified, a negative biopsy and or ureteroscopy is required prior to enrollment
- •Newly suspected, diagnosed, or occasionally recurrent bladder cancer (BC)
- •Note: Occasional recurrence is defined as =< 2 prior NMIBC episodes in the 18 months preceding cystoscopy where the index tumor was identified
- •Participants with single and multiple tumor lesions
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- •Total bilirubin =< 1.5 x institutional upper limit of normal (note: in participants with Gilbert's syndrome, if total bilirubin is > 1.5 x upper limit of normal, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x upper limit of normal, participants may be eligible)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2 × institutional upper limit of normal
- •Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2 × institutional upper limit of normal
- •Urine Culture < 50,000 colonies/cc of 1 or more organisms (if found and treated and a confirmed negative culture obtained off antibiotics before study drug is started, they will be eligible)
- •Serum Testosterone >= 250 ng/dL
- •Thyroid stimulating hormone (TSH) within institutional normal
- •White blood cell count (WBC) >= 0.5 × institutional lower limit of normal
- •The effects of bicalutamide on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, men who are having sex must wear a condom when engaging in any activity that allows for passage of ejaculate to another person throughout the course of the study and 130 days after receiving last dose of study intervention. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak. Additionally, men must agree to not donate sperm for the purpose of reproduction during the study and for a minimum of 130 days after receiving the last dose of study intervention
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Participants who have had a previous exposure to sex hormone (e.g., exogenous androgens) or anti-androgenic therapies (e.g., luteinizing hormone-releasing hormone [LHRH] agonists, LHRH antagonists, 5 alpha reductase-inhibitors, abiraterone or other anti-androgens) within 6 months of accrual
- •Participants taking Coumarin derivative anticoagulation (e.g., warfarin). Other anticoagulation medications are allowed.
- •Participants receiving any other investigational agents.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to bicalutamide.
- •History of prior or concurrent muscle invading UC, or concurrent prostatic urethral, urethral, or upper tract UC or non-urothelial bladder cancer
- •History of radiation therapy to the pelvis, prostate or prostatic bed, or rectum
- •Any condition (uncontrolled intercurrent illness, psychiatric illness, or social situation) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
- •Participants with severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, uncontrolled hypertension, recent arterial or venous thromboembolic events (e.g. pulmonary embolism, cerebrovascular accident including transient ischemic attacks) for which anticoagulation therapy is ongoing, or clinically significant ventricular arrhythmias.
- •In the opinion of the investigator, participant has underlying uncontrolled hypertension, high cholesterol, or diabetes.
- •Allergy or hypersensitivity to bicalutamide, or excipients, unable or unwilling to take ADT.
- •Plans to father a child while enrolled in this study or within 130 days after the last dose of study intervention.
研究组 & 干预措施
Arm 2 (TURBT)
Patients undergo TURBT on day 21. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.
干预措施: Biopsy Procedure (Procedure)
Arm 2 (TURBT)
Patients undergo TURBT on day 21. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.
干预措施: Biospecimen Collection (Procedure)
Arm 2 (TURBT)
Patients undergo TURBT on day 21. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.
干预措施: Questionnaire Administration (Other)
Arm 1 (bicalutamide,TURBT)
Patients receive bicalutamide PO QD on days 1-21. Patients undergo TURBT on day 21. Up to 28 days of bicalutamide prior to TURBT is permitted in the absence of unacceptable toxicity. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.
干预措施: Bicalutamide (Drug)
Arm 1 (bicalutamide,TURBT)
Patients receive bicalutamide PO QD on days 1-21. Patients undergo TURBT on day 21. Up to 28 days of bicalutamide prior to TURBT is permitted in the absence of unacceptable toxicity. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.
干预措施: Biospecimen Collection (Procedure)
Arm 1 (bicalutamide,TURBT)
Patients receive bicalutamide PO QD on days 1-21. Patients undergo TURBT on day 21. Up to 28 days of bicalutamide prior to TURBT is permitted in the absence of unacceptable toxicity. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.
干预措施: Biopsy Procedure (Procedure)
Arm 1 (bicalutamide,TURBT)
Patients receive bicalutamide PO QD on days 1-21. Patients undergo TURBT on day 21. Up to 28 days of bicalutamide prior to TURBT is permitted in the absence of unacceptable toxicity. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.
干预措施: Questionnaire Administration (Other)
Arm 1 (bicalutamide,TURBT)
Patients receive bicalutamide PO QD on days 1-21. Patients undergo TURBT on day 21. Up to 28 days of bicalutamide prior to TURBT is permitted in the absence of unacceptable toxicity. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.
干预措施: Transurethral Resection of Bladder Tumor (Procedure)
Arm 2 (TURBT)
Patients undergo TURBT on day 21. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.
干预措施: Transurethral Resection of Bladder Tumor (Procedure)
结局指标
主要结局
Average Epidermal Growth Factor Receptor (EGFR) expression level
时间窗: Up to 28 days
Will be analyzed as a continuous variable. A two-sample t-test will be conducted to test whether there are significant differences of the log-transformed EGFR expression level (measured by reverse transcriptase polymerase chain reaction \[rtPCR\]) in normal appearing urothelium adjacent to tumor in participants treated with anti-androgen therapy versus (vs.) NSD participants. In case the normality assumption of the two-sample t-test does not hold, Wilcoxon rank-sum test will be performed as a sensitivity analysis. Considering androgen receptor (AR) status can be a treatment effect modifier, a regression analysis will also be performed with the log-transformed EGFR expression level as the outcome and treatment status (bicalutamide or NSD), AR status, and treatment-AR interaction as the predictors.
次要结局
- Effect of apalutamide on EGFR expression(Up to 28 days)
- AR expression in adjacent urothelium(Up to 28 days)
- Toxicity of treatment(Up to 28 days)
- Effect of bicalutamide on EGFR expression(Up to 28 days)