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

NCT00706641 | Completed Results DMC

• 1 other identifier: GU07-122
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

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.

Conditions

Transitional Cell Carcinoma of the Bladder

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• Grade 3/4 Toxicities

  Time of consent through 30 days after treatment discontinuation

• Reduced pSFK Expression

  Baseline to post dasatinib therapy

• Pathologic Complete Response (pCR) Rate

  24 months

• Post-Cystectomy Pathologic Stage

  Staged Post-Cystectomy and dasatinib treatment

• Reduced Ki-67 Expression

  Baseline to post dasatinib therapy

Study Arms (1)

Experimental: Neoadjuvant Dasatinib + Radical Cystectomy

EXPERIMENTAL

Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose

Drug: Dasatinib; Procedure: Radical Cystectomy

Interventions

Dasatinib DRUG

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

Experimental: Neoadjuvant Dasatinib + Radical Cystectomy

Radical Cystectomy 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.

Experimental: Neoadjuvant Dasatinib + Radical Cystectomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoosier Cancer Research Network: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Related 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.

  PMID: 26362343 BACKGROUND

Related Links

• Hoosier Oncology Group Home Page

MeSH Terms

Interventions

Dasatinib; Cystectomy

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Results Point of Contact

• Title: Noah Hahn, MD
• Organization: Hoosier Cancer Research Network, Inc.

jsmith@hoosiercancer.org

317-921-2050

Study Officials

• Noah Hahn, M.D.

  Hoosier Oncology Group, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2008
• First Posted: June 27, 2008
• Study Start: June 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: January 15, 2016
• Results First Posted: January 15, 2016

Record last verified: 2015-12

Locations

US (3)