A Pilot Study of Neoadjuvant Dasatinib Followed by Radical Cystectomy for Transitional Cell Carcinoma of the Bladder
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 3
- 主要终点
- Feasibility
研究概览
简要总结
This pilot study is designed to determine feasibility and safety of treatment with dasatinib administered orally once daily for 4 weeks duration prior to radical cystectomy for urothelial carcinoma of the bladder.
详细描述
OUTLINE: This is a multi-center study.
This is a pilot study designed to determine the safety and feasibility of treatment with dasatinib 100 mg administered orally once daily for 4 weeks duration prior to radical cystectomy for patients with muscle-invasive transitional cell carcinoma of the bladder ineligible for and/or willing to forgo neoadjuvant cisplatin-based combination chemotherapy. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.
ECOG Performance Status 0-1
Life Expectancy: Not specified
Hematopoietic:
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
- •Histological proof of muscle-invasive transitional cell carcinoma of the bladder (stage II-IVa) with no evidence of metastatic disease (focal squamous and/or adenocarcinoma differentiation defined as ≤ 10% of tumor volume allowed, sarcomatoid and small-cell components not allowed). Patient with any degree of fixation of the pelvic sidewall are not eligible.
- •Patients must be willing to undergo a Cystoscopy, prior to registration on study if tumor block is not available.
- •Eligible for radical cystectomy as per the attending urologist.
- •All patients must be willing to forego neoadjuvant cisplatin-based combination chemotherapy and understand it is an option post-surgery or must be deemed ineligible for cisplatin-based combination chemotherapy by the attending medical oncologist.
- •Prior radiation therapy is allowed provided that no radiation therapy was administered to the urinary bladder.
- •Written informed consent and HIPAA authorization for release of personal health information.
- •Age > 18 years at the time of consent.
- •Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4 weeks after treatment discontinuation.
- •Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.
- •Females must not be breastfeeding.
- •Ability to take oral medication (dasatinib must be swallowed whole).
排除标准
- •No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason < grade 7 prostate cancers, or other cancer for which the patient has been disease-free for at least 5 years.
- •No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
- •No prior systemic chemotherapy for transitional cell carcinoma of the bladder( prior intravesical therapy is allowed). Any other prior chemotherapy must have been completed > 5 years prior to initiation of therapy.
- •Following concomitant medications must be discontinued 7 days prior to registration on study and for the duration of dasatinib therapy: Bisphosphonates - due to risk of hypocalcemia; Drugs that are generally accepted to have a risk of causing Torsades de Pointes; any prohibited CYP3A4 inhibitors/inducers/substrates; Anti-coagulation and/or anti-platelet therapies to avoid potential bleeding risks.
- •No clinically significant infections as judged by the treating investigator.
- •No pleural or pericardial effusion of any grade.
- •history of diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
- •No history of diagnosed acquired bleeding disorder (e.g., acquired anti-factor VIII antibodies) within one year prior to registration on protocol therapy.
- •No history of ongoing or recent (within <3 months prior to registration on protocol therapy) significant gastrointestinal bleeding.
- •No known history of hypokalemia that cannot be corrected prior to registration on protocol therapy.
- •No known history of hypomagnesemia that cannot be corrected prior to registration on protocol therapy.
研究组 & 干预措施
Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose
干预措施: Dasatinib (Drug)
Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose
干预措施: Radical Cystectomy (Procedure)
结局指标
主要结局
Feasibility
时间窗: From enrollment to completion of radical cystectomy
Feasibility for this trial is defined as at least 60% (\>=14 of 23) of patients completing study therapy in the absence of Dose Limiting Toxicity (DLT)
次要结局
- Reduced pSFK Expression(Baseline to post dasatinib therapy)
- Grade 3/4 Toxicities(Time of consent through 30 days after treatment discontinuation)
- Pathologic Complete Response (pCR) Rate(24 months)
- Reduced Ki-67 Expression(Baseline to post dasatinib therapy)
- Post-Cystectomy Pathologic Stage(Staged Post-Cystectomy and dasatinib treatment)
- Increase in Cas3 Expression(Baseline to post dasatinib therapy)