- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00706641
Neoadjuvant Dasatinib and Radical Cystectomy for Transitional Cell Carcinoma of the Bladder
A Pilot Study of Neoadjuvant Dasatinib Followed by Radical Cystectomy for Transitional Cell Carcinoma of the Bladder
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Indiana University Simon Cancer Center
-
-
Texas
-
Houston, Texas, United States, 77030
- Baylor College of Medicine
-
-
Virginia
-
Norfolk, Virginia, United States, 23502
- Virginia Oncology Associates
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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
|
Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week)
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Feasibility
Time Frame: From enrollment to completion of radical cystectomy
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Grade 3/4 Toxicities
Time Frame: Time of consent through 30 days after treatment discontinuation
|
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
|
Reduced pSFK Expression
Time Frame: Baseline to post dasatinib therapy
|
pSFK levels were analyzed pre and post treatment
|
Baseline to post dasatinib therapy
|
Pathologic Complete Response (pCR) Rate
Time Frame: 24 months
|
Pathologic complete response (pCR) rate is defined as no residual evidence of muscle-invasive disease at cystectomy (< pT0).
|
24 months
|
Post-Cystectomy Pathologic Stage
Time Frame: Staged Post-Cystectomy and dasatinib treatment
|
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
|
Reduced Ki-67 Expression
Time Frame: Baseline to post dasatinib therapy
|
Ki-67 levels were analyzed pre and post treatment
|
Baseline to post dasatinib therapy
|
Increase in Cas3 Expression
Time Frame: Baseline to post dasatinib therapy
|
Cas3 levels were analyzed pre and post treatment
|
Baseline to post dasatinib therapy
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Noah Hahn, M.D., Hoosier Oncology Group, Inc.
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Urologic Diseases
- Neoplasms, Glandular and Epithelial
- Urinary Bladder Diseases
- Carcinoma
- Urinary Bladder Neoplasms
- Carcinoma, Transitional Cell
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Dasatinib
Other Study ID Numbers
- GU07-122
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Transitional Cell Carcinoma of the Bladder
-
National Cancer Institute (NCI)CompletedMetastatic Transitional Cell Cancer of the Renal Pelvis and Ureter | Recurrent Bladder Cancer | Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter | Stage IV Bladder Cancer | Transitional Cell Carcinoma of the Bladder | Squamous Cell Carcinoma of the BladderUnited States
-
National Cancer Institute (NCI)TerminatedMetastatic Transitional Cell Cancer of the Renal Pelvis and Ureter | Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter | Regional Transitional Cell Cancer of the Renal Pelvis and Ureter | Transitional Cell Carcinoma of the Bladder | Localized Transitional Cell Cancer of the...United States
-
National Cancer Institute (NCI)CompletedMetastatic Transitional Cell Cancer of the Renal Pelvis and Ureter | Recurrent Bladder Cancer | Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter | Regional Transitional Cell Cancer of the Renal Pelvis and Ureter | Stage III Bladder Cancer | Stage IV Bladder Cancer | Transitional...Canada
-
Noah Hahn, M.D.Pfizer; Hoosier Cancer Research NetworkTerminatedTransitional Cell Carcinoma of the BladderUnited States, United Kingdom
-
National Cancer Institute (NCI)TerminatedMetastatic Transitional Cell Cancer of the Renal Pelvis and Ureter | Recurrent Bladder Cancer | Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter | Regional Transitional Cell Cancer of the Renal Pelvis and Ureter | Stage III Bladder Cancer | Stage IV Bladder Cancer | Transitional... and other conditionsUnited States
-
Emory UniversityTerminatedBladder Cancer | Stage III Bladder Cancer | Stage IV Bladder Cancer | Transitional Cell Carcinoma of the Bladder | Squamous Cell Carcinoma of the BladderUnited States
-
National Cancer Institute (NCI)CompletedMetastatic Transitional Cell Cancer of the Renal Pelvis and Ureter | Recurrent Bladder Cancer | Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter | Stage III Bladder Cancer | Stage IV Bladder Cancer | Transitional Cell Carcinoma of the Bladder | Adenocarcinoma of the Bladder | Distal... and other conditionsUnited States
-
Erasmus Medical CenterMerck Sharp & Dohme LLCActive, not recruitingBiomarkers | Transitional Cell Carcinoma of the BladderNetherlands
-
Oncolytics BiotechWithdrawnMuscle-invasive Transitional Cell Carcinoma of the Bladder
-
Lipac Oncology LLCTesoRx Pharma, LLCCompletedUrologic Neoplasms | Urogenital Neoplasms | Urologic Diseases | Urinary Bladder Diseases | Urinary Bladder Neoplasms | Bladder Cancer | Transitional Cell Carcinoma of the Bladder | Non-Muscle Invasive Bladder Cancer | Urinary Bladder | Bladder Cancer Cell TransitionalUnited States
Clinical Trials on Dasatinib
-
Bristol-Myers SquibbCompletedPharmacokinetic Study in Healthy ParticipantsUnited States
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.Completed
-
Hyoung Jin KangNot yet recruitingAcute Lymphoblastic Leukemia, Pediatric
-
National Cancer Institute (NCI)WithdrawnHematopoietic and Lymphoid Cell Neoplasm | Advanced Lymphoma | Advanced Malignant Solid Neoplasm | Refractory Lymphoma | Refractory Malignant Solid Neoplasm | Refractory Plasma Cell MyelomaUnited States
-
National Cancer Institute (NCI)NRG OncologyTerminatedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Clear Cell Cystadenocarcinoma | Endometrial Clear Cell Adenocarcinoma | Recurrent Uterine Corpus CancerUnited States
-
Xspray Pharma ABQPS Bioserve India Pvt LimitedCompleted
-
Peking University Cancer Hospital & InstituteUnknownGastrointestinal Stromal TumorChina
-
Kanto CML Study GroupUnknownMyelogenous Leukemia, Chronic, Chronic PhaseJapan
-
Jonsson Comprehensive Cancer CenterBristol-Myers SquibbCompleted
-
Swiss Group for Clinical Cancer ResearchCompletedGastrointestinal Stromal TumorFrance, Switzerland, Germany, Finland