Phase II Study of Isoflavone G-2535 (Genistein) in Patients With Bladder Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 10
- 主要终点
- Epidermal Growth Factor Receptor (EGFR) Phosphorylation in Tumor Tissue, as Measured by Immunohistochemistry After the Completion of Treatment
研究概览
简要总结
Studying samples of blood, urine, and tissue from patients with cancer in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer. It may also help doctors learn how genistein or placebo works in patients with bladder cancer. This randomized phase II trial is studying genistein or placebo to compare how they work in patients who are undergoing surgery for bladder cancer.
详细描述
PRIMARY OBJECTIVES:
I. To measure the effect of G-2535 on EGF-R phosphorylation. Two EGF-R phosphorylation sites with functional significance are phosphotyrosine 992, which is a direct binding site for the PLC-gamma SH2 domain, and phosphotyrosine 1068, a binding site for the Grb2/SH2 domain. The expression of EGF-R and phosphorylated EGF-R will be determined in tumors as well as adjacent and remote normal appearing urothelium.
SECONDARY OBJECTIVES:
I. Measuring tissue intermediate endpoint biomarkers such as EGF-R mutations (EGFR vIII, exon 19-21), Ki67, activated Caspase 3, Akt, P-Akt, MAP kinase, P-MAP kinase, COX-2, survivin, and BLCA-4 and we will also determine survivin and BLCA-4 levels in urine specimens as surrogate tumor markers. Biomarkers associated with the EGF-R pathway, including Akt and P-Akt will be studied by immunohistochemistry. Additionally, Ki67, activated Caspase 3 (as a marker of apoptosis), and COX-2 will serve as biological endpoint biomarkers to measure the effects of G-2535 on proliferation, apoptosis, and other processes and molecules relevant to bladder cancer. These studies will be performed on tumors as well as adjacent and remote normal urothelium. II. Safety will also be studied.
OUTLINE: This is a randomized, placebo-controlled, multicenter study. Patients are stratified according to invasiveness of disease (non-invasive [stage Ta, Tis, or T1] vs invasive [stage T2, T3, or T4]). Patients are randomized to 1 of 3 treatment arms.
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
- Double (Participant, Investigator)
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
- •Participants eligible for this study will have been evaluated by diagnostic office cystoscopy and found to have a bladder tumor; enrollment (signing of the consent form) must be within 60 days of pre-study cystoscopy demonstrating bladder tumor; the participant should have no evidence of distant metastasis and the primary tumor may represent either an initial diagnosis or recurrent disease of any clinical stage. Study participants must also be candidates for either subsequent cystoscopy/transurethral resection of bladder tumor (TURBT) or complete or partical cystectomy; histologic diagnosis is not required for enrollment; pre-enrollment diagnostic cystoscopy must be at least 45 days after treatment of the bladder with other agents such as BCG (participants with recurrent disease)
- •ECOG performance status 0 or 1
- •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
- •Ability to understand and the willingness to sign a written informed consent document
- •WBC >= 3000/mm^3
- •Platelets >= 100,000mm^3
- •Hemoglobin >= 10 g/dL
- •Bilirubin =< 1.4 mg/dl
- •AST =< 3x normal
- •Creatinine =< 2.0mg/dl
- •Serum calcium =< 10.2 mg/dl,
- •Amylase =< 3 x normal
- •Na >= 125 and =< 155 mmol/L
- •K >= 3.2 and =< 6 mmol/L
- •Cl >= 85 and =< 114 mmol/L
- •CO2 >= 11 mEQ/dL
- •TSH within 1.3 x the upper range of normal and normal T4
- •Females of child-bearing potential must have a negative pregnancy test; patients who have had a bilateral oophorectomy, hysterectomy, are greater than 1 year since their last menses, or are greater than 51 years of age are not considered to be of child-baring potential
- •Participants must agree to stop soy supplements before enrolling in the study
- •Patients must agree to stop taking NSAIDS before enrolling in the study; patients may, however, take cardioprotective doses of aspirin equal to or less than 81mg per day
排除标准
- •Participant may not have received other treatment for bladder cancer between the pre-enrollment cystoscopy and subsequent surgery
- •Participants may not be receiving any other investigational agents
- •Participant may not have received prior pelvic irradiation for any reason
- •Participant may not be receiving concurrent systemic cancer treatment for other cancers
- •Participant may not be taking concurrent soy supplements while on the study medication
- •Participant may not be taking concurrent NSAIDS (aspirin doses of =< 81 mg acceptable) while on the study medication
- •Participant may not be taking thyroid medications
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to genistein, soy isoflavones or other allergies to soy-based products will render a participant ineligible
- •Uncontrolled concurrent illness will render a participant ineligible including, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unregulated cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Women may not be pregnant or lactating; the effects of G-2535 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
研究组 & 干预措施
Arm I (lower dose genistein)
Patients receive oral genistein twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
干预措施: Genistein (Drug)
Arm I (lower dose genistein)
Patients receive oral genistein twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (lower dose genistein)
Patients receive oral genistein twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
干预措施: Pharmacological Study (Other)
Arm I (lower dose genistein)
Patients receive oral genistein twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
干预措施: Therapeutic Conventional Surgery (Procedure)
Arm II (higher dose genistein)
Patients receive oral genistein as in arm I but at a higher dose. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
干预措施: Genistein (Drug)
Arm II (higher dose genistein)
Patients receive oral genistein as in arm I but at a higher dose. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (higher dose genistein)
Patients receive oral genistein as in arm I but at a higher dose. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
干预措施: Pharmacological Study (Other)
Arm II (higher dose genistein)
Patients receive oral genistein as in arm I but at a higher dose. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
干预措施: Therapeutic Conventional Surgery (Procedure)
Arm III (placebo)
Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
干预措施: Laboratory Biomarker Analysis (Other)
Arm III (placebo)
Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
干预措施: Pharmacological Study (Other)
Arm III (placebo)
Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
干预措施: Placebo Administration (Other)
Arm III (placebo)
Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
干预措施: Therapeutic Conventional Surgery (Procedure)
结局指标
主要结局
Epidermal Growth Factor Receptor (EGFR) Phosphorylation in Tumor Tissue, as Measured by Immunohistochemistry After the Completion of Treatment
时间窗: up to 21 days
Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.
pEGFR in Benign Tissue
时间窗: up to 21 days on Study Drug
Detecting the signal of the biomarker, pEGFR, in the benign tissue after being on study drug for between 14-21 days. Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.
次要结局
- Survivin in Tumor Tissue(up to 21 days on Study Drug)
- EGFR in Benign Tissue(up to 21 days on Study Drug)
- Ki-67 in Tumor Tissue(up to 21 days on Study Drug)
- Activated Caspase 3 in Tumor Tissue(up to 21 days on Study Drug)
- COX2 in Tumor Tissue(up to 21 days on Study Drug)
- Survivin in Urine by Visit (pg/ml)(up to 21 days)
- BLCA-4 in Urine by Visit(up to 21 days)
- EGFR Mutations in Tumor Tissue(up to 21 days on Study Drug)
- AKT in Tumor Tissue(up to 21 days on Study Drug)
- MAP Kinase in Tumor Tissue(up to 21 days on Study Drug)
- pMAP Kinase in Tumor Tissue(up to 21 days on Study Drug)
- pAKT in Tumor Tissue(up to 21 days on Study Drug)