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

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT00706641
First received: June 25, 2008
Last updated: March 19, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention
Transitional Cell Carcinoma of the Bladder
Drug: Dasatinib
Procedure: Radical Cystectomy

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • To determine the feasibility of treatment with dasatinib prior to radical cystectomy in patients with muscle invasive transitional cell carcinoma of the bladder. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the safety of treatment with dasatinib prior to radical cystectomy in patients with muscle invasive transitional cell carcinoma of the bladder. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • To evaluate the impact of dasatinib on expression of selected biomarkers. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • To determine the pathologic complete response (pCR) rate. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • To determine the degree of tumor downstaging. [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: June 2008
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00706641

Locations
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
Sponsors and Collaborators
Hoosier Cancer Research Network
Bristol-Myers Squibb
Investigators
Study Chair: Noah Hahn, M.D. Hoosier Oncology Group, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT00706641     History of Changes
Other Study ID Numbers: GU07-122
Study First Received: June 25, 2008
Last Updated: March 19, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Urinary Bladder Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Dasatinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014