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.
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: * Absolute Neutrophil Count (ANC) \> 1.5 K/mm3 * Platelets \> 100 K/mm3 * INR \< 1.2 Hepatic: * Total bilirubin \< 2.0 X Upper Limit of Normal (ULN) * Aspartate aminotransferase (AST) ≤ 2.5 X ULN. * Alanine aminotransferase (ALT ) ≤ 2.5 X ULN Renal: * Serum creatinine \< 2 X ULN Cardiovascular: * No uncontrolled angina, congestive heart failure or MI within 6 months prior to registration on study. * No diagnosed congenital long QT syndrome (a congenital disorder characterized by a prolongation of the QT interval on ECG and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden death). * No history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes). * No prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec), obtained within 28 days prior to being registered on study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week)
Radical cystectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered Dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States
Baylor College of Medicine
Houston, Texas, United States
Virginia Oncology Associates
Norfolk, Virginia, United States
Feasibility
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)
Time frame: From enrollment to completion of radical cystectomy
Grade 3/4 Toxicities
Report grade 3/4 toxicities during treatment with dasatinib prior to radical cystectomy in patients with muscle invasive transitional cell carcinoma of the bladder.
Time frame: Time of consent through 30 days after treatment discontinuation
Reduced pSFK Expression
pSFK levels were analyzed pre and post treatment
Time frame: Baseline to post dasatinib therapy
Pathologic Complete Response (pCR) Rate
Pathologic complete response (pCR) rate is defined as no residual evidence of muscle-invasive disease at cystectomy (\< pT0).
Time frame: 24 months
Post-Cystectomy Pathologic Stage
Tumor Node Metastasis (TNM) Staging. This system classifies tumors by size and extent of the primary tumor (T), involvement of regional lymph nodes (N), and the presence or absence of distant metastases (M) T0=No evidence of primary tumor, Tis=Carcinoma in situ, and T1, T2, T3, T4=Increasing size and/or local extension of the primary tumor, TX=Not assessed N0=No Regional lymph node metastases, N1, N2, N3=Increasing number or extent of regional lymph node involvement, NX=not assessed M0=No distant metastases, M1=Distant metastases present
Time frame: Staged Post-Cystectomy and dasatinib treatment
Reduced Ki-67 Expression
Ki-67 levels were analyzed pre and post treatment
Time frame: Baseline to post dasatinib therapy
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Increase in Cas3 Expression
Cas3 levels were analyzed pre and post treatment
Time frame: Baseline to post dasatinib therapy