Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00706641
Other study ID # GU07-122
Secondary ID
Status Completed
Phase N/A
First received June 25, 2008
Last updated December 10, 2015
Start date June 2008
Est. completion date December 2012

Study information

Verified date December 2015
Source Hoosier Cancer Research Network
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 25
Est. completion date December 2012
Est. primary completion date December 2012
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Dasatinib
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.

Locations

Country Name City State
United States Baylor College of Medicine Houston Texas
United States Indiana University Simon Cancer Center Indianapolis Indiana
United States Virginia Oncology Associates Norfolk Virginia

Sponsors (2)

Lead Sponsor Collaborator
Hoosier Cancer Research Network Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

References & Publications (1)

Hahn NM, Knudsen BS, Daneshmand S, Koch MO, Bihrle R, Foster RS, Gardner TA, Cheng L, Liu Z, Breen T, Fleming MT, Lance R, Corless CL, Alva AS, Shen SS, Huang F, Gertych A, Gallick GE, Mallick J, Ryan C, Galsky MD, Lerner SP, Posadas EM, Sonpavde G. Neoadjuvant dasatinib for muscle-invasive bladder cancer with tissue analysis of biologic activity. Urol Oncol. 2016 Jan;34(1):4.e11-7. doi: 10.1016/j.urolonc.2015.08.005. Epub 2015 Sep 9. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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) From enrollment to completion of radical cystectomy Yes
Secondary 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 of consent through 30 days after treatment discontinuation Yes
Secondary Reduced pSFK Expression pSFK levels were analyzed pre and post treatment Baseline to post dasatinib therapy No
Secondary Pathologic Complete Response (pCR) Rate Pathologic complete response (pCR) rate is defined as no residual evidence of muscle-invasive disease at cystectomy (< pT0). 24 months No
Secondary 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 Staged Post-Cystectomy and dasatinib treatment No
Secondary Reduced Ki-67 Expression Ki-67 levels were analyzed pre and post treatment Baseline to post dasatinib therapy No
Secondary Increase in Cas3 Expression Cas3 levels were analyzed pre and post treatment Baseline to post dasatinib therapy No
See also
  Status Clinical Trial Phase
Completed NCT02897765 - A Personal Cancer Vaccine (NEO-PV-01) w/ Nivolumab for Patients With Melanoma, Lung Cancer or Bladder Cancer Phase 1
Terminated NCT01118351 - Sunitinib Malate in Treating Patients With Recurrent Transitional Cell Bladder Cancer Phase 2
Terminated NCT00112905 - Sorafenib in Treating Patients With Regional or Metastatic Cancer of the Urothelium Phase 2
Completed NCT00072150 - Phase II Trial Of PS-341 (Bortezomib) In Patients With Previously Treated Advanced Urothelial Tract Transitional Cell Carcinoma Phase 2
Completed NCT00028756 - Comparison of Immediate and Delayed Adjuvant Chemotherapy in Treating Patients Who Have Undergone a Radical Cystectomy for Stage III or Stage IV Transitional Cell Carcinoma of the Bladder Urothelium Phase 3
Completed NCT02318329 - Open-Label, Dose-Finding Study Evaluating Safety and PK of FPA144 in Patients With Advanced Solid Tumors Phase 1
Completed NCT00407485 - VEGF Trap in Treating Patients With Recurrent, Locally Advanced, or Metastatic Cancer of the Urothelium Phase 2
Withdrawn NCT01639521 - Gemcitabine Hydrochloride and Cisplatin or High-Dose Methotrexate, Vinblastine, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Urothelial Cancer Phase 2
Completed NCT00003167 - Gene Therapy in Treating Patients With Advanced Bladder Cancer Phase 1
Completed NCT03081858 - Proliposomal Intravesical Paclitaxel for Treatment of Low-Grade, Stage Ta, Non Muscle Invasive Bladder Cancer Phase 1/Phase 2
Completed NCT02101931 - A Laser Detection for Bladder Cancer by (Photodynamic) Spectra of Urine Phase 3
Terminated NCT00859339 - Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy for TCC Phase 2
Completed NCT00005831 - Trastuzumab and Combination Chemotherapy in Treating Patients With Locally Recurrent or Metastatic Urinary Tract Cancer Phase 2
Completed NCT01824329 - Prostate Capsule Sparing Cystectomy and Nerve-sparing Radical Cystoprostatectomy in Men With Bladder Cancer Phase 2
Terminated NCT00363883 - Vorinostat in Treating Patients With Locally Recurrent or Metastatic Cancer of the Urothelium Phase 2
Completed NCT00021099 - Ixabepilone in Treating Patients With Advanced Urinary Tract Cancer Phase 2
Terminated NCT01382706 - Docetaxel and Lapatinib in Metastatic Transitional Cell Carcinoma in Bladder Phase 2
Terminated NCT01954173 - Adjuvant Radiation for High Risk Bladder Cancer N/A
Terminated NCT00004856 - Trastuzumab in Treating Patients With Previously Treated, Locally Advanced, or Metastatic Cancer of the Urothelium Phase 2
Terminated NCT01282333 - Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer Phase 1