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CompletedNCT00706641Updated Jan 15, 2016Results posted

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

An interventional study of Dasatinib and Radical Cystectomy in Transitional Cell Carcinoma of the Bladder, sponsored by Hoosier Cancer Research Network. Completed at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-01-15.

Sponsored by Hoosier Cancer Research Network · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
25
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.
02

Conditions studied

  • Transitional Cell Carcinoma of the Bladder
03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 25 is below the median of 45 across 5,170 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

Hoosier Cancer Research Network is the lead sponsor of 27 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
25 participants (actual)

Study arms

  • 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

    Drug: Dasatinib · Procedure: Radical Cystectomy

Interventions

  • DrugDasatinib

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

  • ProcedureRadical 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.

06

What researchers measure

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)

    Time frame: From enrollment to completion of radical cystectomy

Secondary outcomes

  1. 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 frame: Time of consent through 30 days after treatment discontinuation

  2. Reduced pSFK Expression

    pSFK levels were analyzed pre and post treatment

    Time frame: Baseline to post dasatinib therapy

  3. Pathologic Complete Response (pCR) Rate

    Pathologic complete response (pCR) rate is defined as no residual evidence of muscle-invasive disease at cystectomy (\< pT0).

    Time frame: 24 months

  4. 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

    Time frame: Staged Post-Cystectomy and dasatinib treatment

  5. Reduced Ki-67 Expression

    Ki-67 levels were analyzed pre and post treatment

    Time frame: Baseline to post dasatinib therapy

  6. Increase in Cas3 Expression

    Cas3 levels were analyzed pre and post treatment

    Time frame: Baseline to post dasatinib therapy

07

Results

Posted Jan 15, 2016

Participant flow

Dasatinib Administration
Participant flow — Dasatinib Administration
MilestoneExperimental: Neoadjuvant Dasatinib + Radical Cystectomy
Started25
Toxicity evaluation24
Completed23
Not completed2
Withdrew: Withdrawal by subject1
Withdrew: Ineligible after start of therapy1
Radical Cystectomy
Participant flow — Radical Cystectomy
MilestoneExperimental: Neoadjuvant Dasatinib + Radical Cystectomy
Started23
Completed22
Not completed1
Withdrew: Deemed unresectable upon exploration1

Outcome measures

PrimaryFeasibility

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)

Time frame:
From enrollment to completion of radical cystectomy
Reported as:
Number · participants
Feasibility
participantsExperimental: Neoadjuvant Dasatinib + Radical Cystectomy
DLT8
Absence of DLT15
SecondaryGrade 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 frame:
Time of consent through 30 days after treatment discontinuation
Reported as:
Number · percentage of particpants
Grade 3/4 Toxicities
percentage of particpantsExperimental: Neoadjuvant Dasatinib + Radical Cystectomy
Anemia4
Fatigue8
Diarrhea4
Nausea4
Anorexia4
Abdominal Pain4
Dyspnea8
Hematuria4
Superventricular and Nodal Arrythmia4
Enteric Fistula8
Deep Vein Thrombosis \ Pulmonary Embolism8
SecondaryReduced pSFK Expression

pSFK levels were analyzed pre and post treatment

Time frame:
Baseline to post dasatinib therapy
Reported as:
Number · participants
Reduced pSFK Expression
participantsExperimental: Neoadjuvant Dasatinib + Radical Cystectomy
Reduced pSFK Expression16
Statistical analysis
  • Experimental: Neoadjuvant Dasatinib + Radical Cystectomy · paired t-test · p = 0.003
SecondaryPathologic Complete Response (pCR) Rate

Pathologic complete response (pCR) rate is defined as no residual evidence of muscle-invasive disease at cystectomy (\< pT0).

Time frame:
24 months
Reported as:
Number · participants
Pathologic Complete Response (pCR) Rate
participantsExperimental: Neoadjuvant Dasatinib + Radical Cystectomy
Pathologic Complete Response (pCR) Rate0
SecondaryPost-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

Time frame:
Staged Post-Cystectomy and dasatinib treatment
Reported as:
Number · percentage of particpants
Post-Cystectomy Pathologic Stage
percentage of particpantsExperimental: Neoadjuvant Dasatinib + Radical Cystectomy
T1\Tis23 (10 to 44)
T227 (13 to 48)
T341 (23 to 61)
T49 (1 to 29)
Unresectable5 (0 to 24)
SecondaryReduced Ki-67 Expression

Ki-67 levels were analyzed pre and post treatment

Time frame:
Baseline to post dasatinib therapy
Reported as:
Number · participants
Reduced Ki-67 Expression
participantsExperimental: Neoadjuvant Dasatinib + Radical Cystectomy
Reduced Ki-67 Expression4
Statistical analysis
  • Experimental: Neoadjuvant Dasatinib + Radical Cystectomy · paired t-test · p = 0.20
SecondaryIncrease in Cas3 Expression

Cas3 levels were analyzed pre and post treatment

Time frame:
Baseline to post dasatinib therapy
Reported as:
Number · participants
Increase in Cas3 Expression
participantsExperimental: Neoadjuvant Dasatinib + Radical Cystectomy
Increase in Cas3 Expression3
Statistical analysis
  • Experimental: Neoadjuvant Dasatinib + Radical Cystectomy · paired t-test · p = 0.42

Adverse events

Collected over Duration of Study. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Experimental: Neoadjuvant Dasatinib + Radical Cystectomy—4/25 (16%)24/25 (96%)
Most frequent serious events
Showing 10 of 11
Most frequent serious events
EventExperimental: Neoadjuvant Dasatinib + Radical Cystectomy
ESOPHAGITISGastrointestinal disorders1/25
FISTULA, GI / ANUSGastrointestinal disorders1/25
HEMORRHAGE, GI / PERITONEAL CAVITYGastrointestinal disorders1/25
HYPERTENSIONCardiac disorders1/25
HYPOTENSIONCardiac disorders1/25
LEAK (INCLUDING ANASTOMOTIC), GI / SMALL BOWELGastrointestinal disorders1/25
PALPITATIONSCardiac disorders1/25
SUPRAVENTRICULAR AND NODAL ARRHYTHMIA / ATRIAL FLUTTERCardiac disorders1/25
THROMBOSIS/EMBOLISM (VASCULAR ACCESS-RELATED)Vascular disorders1/25
THROMBOSIS/THROMBUS/EMBOLISMVascular disorders1/25
Most frequent other events
Showing 10 of 101
Most frequent other events
EventExperimental: Neoadjuvant Dasatinib + Radical Cystectomy
FATIGUE (ASTHENIA, LETHARGY, MALAISE)General disorders22/25
NAUSEAGastrointestinal disorders14/25
CONSTIPATIONGastrointestinal disorders13/25
DIARRHEAGastrointestinal disorders13/25
ANOREXIAGastrointestinal disorders12/25
HEARTBURN/DYSPEPSIAGastrointestinal disorders11/25
PAIN / ABDOMEN NOSGastrointestinal disorders8/25
RENAL/GENITOURINARY - OTHER (SPECIFY, __)Renal and urinary disorders8/25
PAIN - OTHER (SPECIFY, __)General disorders7/25
URINARY FREQUENCY/URGENCYRenal and urinary disorders7/25

Baseline characteristics

All subjects who started treatment on dastanib were included for age, gender, and ECOG PS characteristics. One patient was removed from the study because they were found to be ineligible based on histology after they started treatment and thus were not included in the T-Stage characteristics.

Age, Continuous
Age, Continuous(years)Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Median62 (47 to 83)
Sex: Female, Male
Sex: Female, Male(Participants)Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Female5
Male20
ECOG PS
ECOG PS(participants)Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
ECOG PS 019
ECOG PS 16
T-Stage at Study Entry
T-Stage at Study Entry(participants)Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
T217
T37
T4a0
08

Study locations

3 sites
  • Indiana University Simon Cancer Center
    Indianapolis, Indiana 46202, United States
  • Baylor College of Medicine
    Houston, Texas 77030, United States
  • Virginia Oncology Associates
    Norfolk, Virginia 23502, United States
09

References and documents

Publications

  • 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. PubMed 26362343 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 15, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00706641
Lead sponsor
Hoosier Cancer Research Network
Collaborators
Bristol-Myers Squibb
Responsible party
Sponsor
First posted
Jun 27, 2008
Start date
Jun 2008
Primary completion
Dec 2012
Completion
Dec 2012
Results posted
Jan 15, 2016
Last update
Jan 15, 2016

Study contacts

Noah Hahn, M.D.
study chair · Hoosier Oncology Group, Inc.

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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