Neoadjuvant Dasatinib and Radical Cystectomy for Transitional Cell Carcinoma of the Bladder
Neoadjuvant Dasatinib and Radical Cystectomy for Transitional Cell Carcinoma of the Bladder
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.
Inclusion Criteria:

 -  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).

 Exclusion Criteria:

 -  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.