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

NCT ID: NCT00706641

Last Updated: 2016-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2012-12-31

Brief 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.

Detailed 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.

Conditions

Transitional Cell Carcinoma of the Bladder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Dasatinib

Intervention Type: DRUG

Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week)

Radical Cystectomy

Intervention Type: PROCEDURE

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.

Interventions

Dasatinib

Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week)

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Hoosier Cancer Research Network

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Noah Hahn, M.D.

Role: STUDY_CHAIR

Hoosier Oncology Group, Inc.

Locations

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

Baylor College of Medicine

Houston, Texas, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 26362343 (View on PubMed)

Related Links

http://www.hoosieroncologygroup.org

Hoosier Oncology Group Home Page

Other Identifiers

GU07-122

Identifier Type: -

Identifier Source: org_study_id