Neoadjuvant Dasatinib and Radical Cystectomy for Transitional Cell Carcinoma of the Bladder
Transitional Cell Carcinoma of the Bladder
Procedure: Radical Cystectomy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Neoadjuvant Dasatinib Followed by Radical Cystectomy for Transitional Cell Carcinoma of the Bladder|
- Feasibility [ Time Frame: From enrollment to completion of radical cystectomy ] [ Designated as safety issue: Yes ]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)
- Grade 3/4 Toxicities [ Time Frame: Time of consent through 30 days after treatment discontinuation ] [ Designated as safety issue: Yes ]Report grade 3/4 toxicities during treatment with dasatinib prior to radical cystectomy in patients with muscle invasive transitional cell carcinoma of the bladder.
- Reduced pSFK Expression [ Time Frame: Baseline to post dasatinib therapy ] [ Designated as safety issue: No ]pSFK levels were analyzed pre and post treatment
- Pathologic Complete Response (pCR) Rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]Pathologic complete response (pCR) rate is defined as no residual evidence of muscle-invasive disease at cystectomy (< pT0).
- Post-Cystectomy Pathologic Stage [ Time Frame: Staged Post-Cystectomy and dasatinib treatment ] [ Designated as safety issue: No ]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
- Reduced Ki-67 Expression [ Time Frame: Baseline to post dasatinib therapy ] [ Designated as safety issue: No ]Ki-67 levels were analyzed pre and post treatment
- Increase in Cas3 Expression [ Time Frame: Baseline to post dasatinib therapy ] [ Designated as safety issue: No ]Cas3 levels were analyzed pre and post treatment
|Study Start Date:||June 2008|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: 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
Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week)Procedure: Radical Cystectomy
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.
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
- Absolute Neutrophil Count (ANC) > 1.5 K/mm3
- Platelets > 100 K/mm3
- INR < 1.2
- Total bilirubin < 2.0 X Upper Limit of Normal (ULN)
- Aspartate aminotransferase (AST) ≤ 2.5 X ULN.
- Alanine aminotransferase (ALT ) ≤ 2.5 X ULN
- Serum creatinine < 2 X ULN
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00706641
|United States, Indiana|
|Indiana University Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|United States, Virginia|
|Virginia Oncology Associates|
|Norfolk, Virginia, United States, 23502|
|Study Chair:||Noah Hahn, M.D.||Hoosier Oncology Group, Inc.|