Transitional Cell Carcinoma of the BladderNCT00706641
Neoadjuvant Dasatinib and Radical Cystectomy for Transitional Cell Carcinoma of the Bladder
A study testing Dasatinib and Radical Cystectomy in people with Transitional Cell Carcinoma of the Bladder, run by Hoosier Cancer Research Network at 3 sites in United States.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transitional Cell Carcinoma of the Bladder
- What is being tested?
- Dasatinib and Radical Cystectomy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 3 sitesUnited States
- Study dates
- Jun 2008to Dec 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Baylor College of Medicine
Houston, Texas, 77030
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
Virginia Oncology Associates
Norfolk, Virginia, 23502
About this study
Official title: A Pilot Study of Neoadjuvant Dasatinib Followed by Radical Cystectomy for Transitional Cell Carcinoma of the Bladder
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.
- Being tested
- Dasatinib, Radical Cystectomy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week)
Radical CystectomyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Dasatinib; Procedure: Radical Cystectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: From enrollment to completion of radical cystectomy
Secondary outcomes (6)
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.
Measured: Time of consent through 30 days after treatment discontinuation
Reduced pSFK Expression
pSFK levels were analyzed pre and post treatment
Measured: Baseline to post dasatinib therapy
Pathologic Complete Response (pCR) Rate
Pathologic complete response (pCR) rate is defined as no residual evidence of muscle-invasive disease at cystectomy (< pT0).
Measured: 24 months
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
Measured: Staged Post-Cystectomy and dasatinib treatment
Reduced Ki-67 Expression
Ki-67 levels were analyzed pre and post treatment
Measured: Baseline to post dasatinib therapy
Increase in Cas3 Expression
Cas3 levels were analyzed pre and post treatment
Measured: Baseline to post dasatinib therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2008 (estimated)
- Study startJun 2008
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Transitional Cell Carcinoma of the BladderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoosier Cancer Research Network
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Noah Hahn, M.D., Study chair, Hoosier Oncology Group, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00706641
- Sponsor's protocol ID
- GU07-122
- Status last verified
- Dec 2015
- First submitted
- 25 Jun 2008
- Last updated
- 15 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Neoadjuvant Dasatinib Followed by Radical Cystectomy for Transitional Cell Carcinoma of the Bladder
- ClinicalTrials.gov ID
- NCT00706641
- Acronym / sponsor ID
- GU07-122
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Hoosier Cancer Research NetworkUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Jun 2008
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 27 Jun 2008 (estimated)
- Results
- Posted 15 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: Neoadjuvant Dasatinib + Radical Cystectomy | Experimental | Drug: Dasatinib, Procedure: Radical CystectomyDasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DasatinibDasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week) | Drug | Experimental: Neoadjuvant Dasatinib + Radical Cystectomy |
| Radical CystectomyRadical 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. | Procedure or surgery | Experimental: Neoadjuvant Dasatinib + Radical Cystectomy |
Primary outcome
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)
6 secondary outcomes
Grade 3/4 Toxicities
Time frame: Time of consent through 30 days after treatment discontinuation
Reduced pSFK Expression
Time frame: Baseline to post dasatinib therapy
Pathologic Complete Response (pCR) Rate
Time frame: 24 months
Post-Cystectomy Pathologic Stage
Time frame: Staged Post-Cystectomy and dasatinib treatment
Reduced Ki-67 Expression
Time frame: Baseline to post dasatinib therapy
Increase in Cas3 Expression
Time frame: Baseline to post dasatinib therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26362343Hahn 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.
- Hoosier Oncology Group Home PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Noah Hahn, M.D. study chair
Hoosier Oncology Group, Inc.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dasatinib and Radical Cystectomy in people with Transitional Cell Carcinoma of the Bladder, run by Hoosier Cancer Research Network at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility (time frame: From enrollment to completion of radical cystectomy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00706641, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2016.