A Phase 1-2 Study of Rapamycin and Cisplatin/Gemcitabine for Treatment of Patients With Bladder Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Percent of Patients With Pathologic Complete Response (Phase II)
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of sirolimus when given together with cisplatin and gemcitabine hydrochloride and to see how well they work in treating patients with bladder cancer. Biological therapies, such as sirolimus, may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cisplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving sirolimus together with cisplatin and gemcitabine hydrochloride may be an effective treatment for bladder cancer.
详细描述
PRIMARY OBJECTIVES:
I. To define the maximum-tolerated dose (MTD) of sirolimus (rapamycin) combined with gemcitabine hydrochloride and cisplatin (GC). (Phase I)
II. To determine the pathologic complete response rate at cystectomy in patients with localized, muscle invasive carcinoma of the bladder (clinical tumor [T]2-4, node [N]0 or N1). (Phase II)
SECONDARY OBJECTIVES:
I. To assess the response rate to rapamycin combined with GC. (Phase I)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information
- •Histologically or cytologically confirmed carcinoma of the bladder of all histologies except neuroendocrine differentiation or squamous cell histology
- •Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
- •Eligibility for phase 1 and phase 2 components:
- •Phase 1 - clinical T3 or T4 or N1 or M1 cancer which is untreated or previously treated with platinum based therapy with primary tumor still present in the bladder and amenable to sampling before and after treatment, as indicated
- •Phase 2 - clinical T2-4 N0 or N1 untreated with primary tumor still present in the bladder and amenable to sampling before and after treatment, as indicated
- •Life expectancy >= 12 weeks
- •No prior malignancy is allowed except:
- •Adequately treated basal cell or squamous cell skin cancer or
- •In situ carcinoma of any site or
- •Other adequately treated malignancy for which the patient is currently disease free for at least one year
- •Absolute neutrophil count >= 1.5 x 10^9 cells/L
- •Hemoglobin (Hgb) >= 9.0 g/dL
- •Platelets >= 100,000 x 10^9/L
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 1.5 x upper limit of normal (ULN)
- •Bilirubin and total bilirubin levels =< 1.5 x ULN
- •Serum creatinine < 1.5 X institutional ULN mg/dL OR glomerular filtration rate (GFR) >= 50 mL/min
- •All pre-study labs required for determination of eligibility are to be completed within 30 days prior to day -2 (or the next business day if falls on a weekend or holiday)
- •X-rays and/or scans to assess all disease sites are to be completed within 30 days prior to day -2 (or the next business day if falls on a weekend or holiday)
排除标准
- •Patients currently receiving active therapy for other neoplastic disorders
- •Known parenchymal brain metastasis
- •Active or symptomatic viral hepatitis or chronic liver disease
- •Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) class II-IV heart disease or cardiac ejection fraction measurement of < 45 % at baseline, if done
- •Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy
- •Administration of an investigational therapeutic within 30 days of cycle 1, day 1
- •Patients with dementia/psychiatric illness/social situations that would limit compliance with study requirements or would prohibit the understanding and/or giving of informed consent
- •Patients with medical conditions, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained will not be eligible
- •Any condition which, in the opinion of the investigator, would preclude participation in this trial
研究组 & 干预措施
Sirolimus, cisplatin, gemcitabine
Sirolimus day -2, cisplatin 70 mg/m2 IV Day 1 and gemcitabine hydrochloride 1000 mg/m2 IV days 1 and 8 every 21 days for 4 cycles followed by cystectomy (surgery)
干预措施: Cisplatin (Drug)
Sirolimus, cisplatin, gemcitabine
Sirolimus day -2, cisplatin 70 mg/m2 IV Day 1 and gemcitabine hydrochloride 1000 mg/m2 IV days 1 and 8 every 21 days for 4 cycles followed by cystectomy (surgery)
干预措施: Gemcitabine Hydrochloride (Drug)
Sirolimus, cisplatin, gemcitabine
Sirolimus day -2, cisplatin 70 mg/m2 IV Day 1 and gemcitabine hydrochloride 1000 mg/m2 IV days 1 and 8 every 21 days for 4 cycles followed by cystectomy (surgery)
干预措施: Sirolimus (Drug)
Sirolimus, cisplatin, gemcitabine
Sirolimus day -2, cisplatin 70 mg/m2 IV Day 1 and gemcitabine hydrochloride 1000 mg/m2 IV days 1 and 8 every 21 days for 4 cycles followed by cystectomy (surgery)
干预措施: Cystectomy (Procedure)
结局指标
主要结局
Percent of Patients With Pathologic Complete Response (Phase II)
时间窗: 12 weeks
The study will follow an optimal two-stage Simon design based on pathologic complete response rate.
Patients With Dose Limiting Toxicity
时间窗: Up to 28 days
Safety will be assessed through summaries of adverse events, vital signs, physical examinations, and clinical laboratory test data (including change from baseline).
次要结局
- Incidence of Adverse Events Including Any Unfavorable and Unintended Sign, Symptom, Diagnosis, or Disease Temporally Associated With the Use of a Medicinal Product, Whether or Not Related to the Medicinal Product (Phase I and II)(Up to 28 days after completion of study treatment)
研究者
Bruce Montgomery
Principal Investigator
University of Washington