Neoadjuvant Dasatinib and Radical Cystectomy for Transitional Cell Carcinoma of the Bladder

Hoosier Cancer Research Network

Status

Completed

Conditions

Transitional Cell Carcinoma of the Bladder

Treatments

Procedure: Radical Cystectomy

Drug: Dasatinib

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00706641

GU07-122

Details and patient eligibility

About

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.

Full description

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.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.