Urinary Tract Urothelial CarcinomaPhase 2SutentNCT00794950
Bacillus Calmette-Guerin Followed by Sunitinib for the Treatment of High Risk Non-muscle Invasive Lower Urinary Tract Urothelial Carcinoma
A Phase 2 study testing Sunitinib in people with Urinary Tract Urothelial Carcinoma, run by University of Michigan at 2 sites in United States.
Trial summary
A majority of patients with bladder cancer have disease confined to the inner lining of the bladder. Patients with high risk features (high grade tumors, tumors invading into a deeper superficial layer) are routinely treated with Bacillus Calmette Guerin (BCG) instilled in their bladder after the tumor has been… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urinary Tract Urothelial Carcinoma
- What is being tested?
- Sunitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2009to 22 Aug 2016
- Phase
- Phase 2
- 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
- Patients must have histologically confirmed urothelial carcinoma confined to the urinary bladder and/or prostatic urethra by bladder biopsy within 6 weeks of study enrollment.
- Patients are eligible if the biopsy was done within 3 months of enrollment and a cystoscopy demonstrates no gross disease within 6 weeks of enrollment.
- Tumor histology with >50% transitional cell carcinoma histology
- Tumor stage less than or equal to T1 confirmed by pathology report
- Patients with a T1 tumor will require a restaging TURBT confirming no higher stage tumor prior to study enrollment
- High grade tumor as defined by the WHO/ISUP 1998 classification system. (Presence of carcinoma in situ constitutes a high grade tumor)
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- No BCG within 12 months of enrollment
- Patients are allowed to have received a single dose of intravesical chemotherapy (excluding BCG) in the operating room following transurethral resection documenting non-muscle invasive urothelial carcinoma of the lower urinary tract.
- Patients are allowed to have received a previous 6 week cycle of any standard intravesical chemotherapy if > 3 months prior to enrollment.
- Age >18 years.
- ECOG performance status 0 or 1
- Patients must have adequate organ and marrow function as defined below:
- absolute neutrophil count > 1,500/mcL
- platelets > 100,000/mcL
- total bilirubin less than or equal to 1.5 upper limit of normal
- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper
- limit of normal
- Serum creatinine < 2.0 mg/dl
- MUGA scan within institutional normal limits
- Timing guideline for pre-study labs and measurements:
- All pre-study labs required for determination of eligibility are to be completed within 6 weeks prior to registration.
- X-rays and/or scans to determine disease status are to be completed within 6 months prior to registration (or the next business day if falls on a weekend or holiday).
Who cannot join
- Patients with a prior history of radiation for bladder cancer
- Patients with a prior history of radiation for prostate cancer are eligible for the study
- Greater than or equal to T2N0M0 transitional cell carcinoma of the bladder on current pathology or in the past
- Patients with a prior history of upper tract urothelial carcinoma are eligible for participation in the study as long as there is no evidence of disease for 6 months prior to study enrollment
- Patients with other malignancies are eligible for enrollment in the study but should not be on active treatment for this malignancy within 12 months of study enrollment. Patients with prior history of local treatment for prostate cancer are eligible for participation in the study
- Patients cannot have received Sunitinib or other anti-angiogenic therapy for at least 12 months prior to enrollment in the study
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- History of allergic reactions attributed to compounds of similar chemical or biologic composition to BCG and Sunitinib
- Patients with prior systemic infection with BCG are not eligible for the study
- Patients with prior intolerance to BCG may be considered
- Major incisional surgery within 4 weeks of study enrollment
- Bleeding diathesis or unresolved gross hematuria after bladder biopsy
- Known HIV - positive patients may not participate. This is to avoid additional complications that immune suppression and HIV infection may cause due to treatment with BCG, which is a live attenuated bacteria that is known to cause systemic infection in patients who are immunocompromised.
- Patients taking agents that result in immunosuppression are not eligible for the study due to the potential for the increased risk of systemic infection in those patients receiving BCG
- Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF), cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
- Ongoing cardiac dysrhythmias of NCI CTCAE grade 2.
- Patients with history of or who are suspected to have CHF can be included as long as they are asymptomatic and have an ejection fraction that is equal to or above the institutional lower limit of normal by baseline MUGA (obtained within 28 days of registration or the next business day if falls on a weekend or holiday).
- QTc interval > 500 msec on baseline EKG (to be done within 6 weeks prior to registration or the next business day if falls on a weekend or holiday).
- Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal medical therapy).
- Patient may not have unresolved bacterial infection.
- Patients with hypothyroidism that can not be adequately controlled with medication will be excluded. All patients will be monitored at trial initiation with a TSH.
- Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.
- Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy.
- All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment.
- Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy.
- The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Alon Weizer, MD
Ann Arbor, Michigan, 48109
Mark P. Schoenberg, MD
Baltimore, Maryland, 21287-2101
About this study
Official title: A Phase II Study of Intravesical Bacillus Calmette-Guerin Followed by Sunitinib for the Treatment of High Risk Non-muscle Invasive Lower Urinary Tract Urothelial Carcinoma
A majority of patients with bladder cancer have disease confined to the inner lining of the bladder. Patients with high risk features (high grade tumors, tumors invading into a deeper superficial layer) are routinely treated with Bacillus Calmette Guerin (BCG) instilled in their bladder after the tumor has been removed. While up to 55% of patients respond to BCG, failure to respond may suggest a more aggressive tumor that requires more definitive therapy with complete bladder removal. BCG is believed to work by stimulating the body's own immune system to attack tumor cells. It may also work by blocking the machinery that tumors use to grow blood vessels which fuel tumor growth. A newer oral drug, sunitinib has shown to help patients with metastatic bladder cancer by blocking new blood vessel growth (VEGF inhibition). The investigators are studying the use of BCG followed by sunitinib in patients with high risk non-muscle invasive bladder cancer to evaluate the complete response (no visible evidence of tumor in the bladder) at 3 months and 6 months. The investigators will also evaluate whether there is recurrent tumor at three years.
Read the detailed description
Despite a complete response of 45-55% in patients with non-muscle invasive urothelial carcinoma involving the lower urinary tract at 3 months, many patients suffer from multiple recurrences and progression in up to 1/3 of patients. While radical cystectomy is an effective local therapy for patients with high risk non-invasive disease, roughly 15% of patients will still develop progression. More importantly, the morbidity of radical cystectomy as described above represents a barrier to treatment in some individuals. Thus, there is a real need to identify newer therapies that reduce morbidity and improve outcomes in patients with non-invasive urothelial cancer. While multiple drug regimens have been the standard for many forms of cancer including invasive bladder cancer, few reports exist on multidrug regimens for non-invasive bladder cancer.
The fundamentally agreed upon mechanism of action of BCG intravesical therapy for superficial bladder cancer is the generation of a non-specific immune response with the expression of cytokines by inflammatory cells resulting in tumor death. Cytokines produced by BCG therapy such as IFNα may block vascular endothelial growth factor (VEGF) which is expressed in superficial and invasive bladder cancer and may provide a mechanism for disease progression.
Sunitinib is an oral tyrosine kinase inhibitor that blocks VEGF. Recent reports demonstrate clinical response in patients with metastatic bladder cancer treated with sunitinib after recurrence following standard chemotherapeutic regimens. The addition of sunitinib following BCG in order to consolidate VEGF inhibition may result in superior 3 month complete response rates. We know that patients who have a complete response to BCG at 3 months have improved disease.
- Conditions
- Urinary Tract Urothelial Carcinoma
- Being tested
- Sunitinib
- Keywords
- Bladder Cancer, High Risk Non-muscle Invasive Lower Urinary Tract Urothelial Carcinoma
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
Also called Sutent
Patients are treated with a 6-week induction course of intravesical bacillus Calmette-Guerin (BCG) followed by a 2 week rest period and 4 week course of oral Sunitinib.
Patients will receive intravesical BCG (81 mg Theracys BCG in 50 ml normal saline) once weekly for 6 weeks within 6 weeks of bladder biopsy confirming high risk non-muscle invasive urothelial carcinoma. Two weeks after completion of BCG, patients will receive Sunitinib (50 mg daily) continuously for 28 days followed by a two week rest period. Patients will be reassessed with transurethral resection and urine cytology. Those with residual/recurrent disease will receive a second course identical to the initial protocol. Those with a complete response following initial or second treatment will be placed on maintenance BCG (3 week course every 6 months for 2 years). Those failing (progression, intolerance) initial/secondary treatments will be offered alternative therapy.
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib treatment | Experimental | Intravesical BCG (81 mg Theracys BCG in 50 ml normal saline) once weekly for 6 weeks within 6 weeks of bladder biopsy confirming high risk non-muscle invasive urothelial carcinoma. Receives: Drug: Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Complete Response at 3 Months
Complete response is defined as no evidence of cancer on bladder biopsy or on a urine test that looks for cancer cells (cytology)
Measured: 14 weeks
Secondary outcomes (3)
Percentage of Participants Who Experienced a Complete Response at 6 Months, Following Study Regimen.
Complete response is defined as no evidence of cancer on bladder biopsy or on a urine test that looks for cancer cells (cytology)
Measured: 28 weeks
Recurrence-free Survival at 2 Years in Patients With Intact Bladder.
Measured: 2 years
Number of Participants With Toxicity Related to Treatment With BCG Followed by Sunitinib
Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to characterize the toxicity: Toxic events are listed by name, body system and grade.
Note: to fit within character length constraints, "3" below means Grade 3; and S \& S means Skin and Subcutaneous system.
Measured: 26 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2008 (estimated)
- Study startJan 2009
- Primary completion22 Aug 2016
- Study completion22 Aug 2016
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.
- Other trials for Urinary Tract Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alon Weizer, University of Michigan
- Investigators
- Alon Weizer, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00794950
- Sponsor's protocol ID
- Sutent V5 / November 9, 2009
- Acronym
- Sutent
- Status last verified
- Sep 2019
- First submitted
- 20 Nov 2008
- Last updated
- 23 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Intravesical Bacillus Calmette-Guerin Followed by Sunitinib for the Treatment of High Risk Non-muscle Invasive Lower Urinary Tract Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT00794950
- Acronym / sponsor ID
- Sutent / Sutent V5 / November 9, 2009
- Conditions
- Urinary Tract Urothelial Carcinoma
- Keywords
- Bladder Cancer, High Risk Non-muscle Invasive Lower Urinary Tract Urothelial Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Study start
- Jan 2009 (actual)
- Primary completion
- 22 Aug 2016 (actual)
- Study completion
- 22 Aug 2016 (actual)
- First posted
- 21 Nov 2008 (estimated)
- Results
- Posted 23 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A majority of patients with bladder cancer have disease confined to the inner lining of the bladder. Patients with high risk features (high grade tumors, tumors invading into a deeper superficial layer) are routinely treated with Bacillus Calmette Guerin (BCG) instilled in their bladder after the tumor has been removed. While up to 55% of patients respond to BCG, failure to respond may suggest a more aggressive tumor that requires more definitive therapy with complete bladder removal. BCG is believed to work by stimulating the body's own immune system to attack tumor cells. It may also work by blocking the machinery that tumors use to grow blood vessels which fuel tumor growth. A newer oral drug, sunitinib has shown to help patients with metastatic bladder cancer by blocking new blood vessel growth (VEGF inhibition). The investigators are studying the use of BCG followed by sunitinib in patients with high risk non-muscle invasive bladder cancer to evaluate the complete response (no visible evidence of tumor in the bladder) at 3 months and 6 months. The investigators will also evaluate whether there is recurrent tumor at three years.
Detailed description
Despite a complete response of 45-55% in patients with non-muscle invasive urothelial carcinoma involving the lower urinary tract at 3 months, many patients suffer from multiple recurrences and progression in up to 1/3 of patients. While radical cystectomy is an effective local therapy for patients with high risk non-invasive disease, roughly 15% of patients will still develop progression. More importantly, the morbidity of radical cystectomy as described above represents a barrier to treatment in some individuals. Thus, there is a real need to identify newer therapies that reduce morbidity and improve outcomes in patients with non-invasive urothelial cancer. While multiple drug regimens have been the standard for many forms of cancer including invasive bladder cancer, few reports exist on multidrug regimens for non-invasive bladder cancer.
The fundamentally agreed upon mechanism of action of BCG intravesical therapy for superficial bladder cancer is the generation of a non-specific immune response with the expression of cytokines by inflammatory cells resulting in tumor death. Cytokines produced by BCG therapy such as IFNα may block vascular endothelial growth factor (VEGF) which is expressed in superficial and invasive bladder cancer and may provide a mechanism for disease progression.
Sunitinib is an oral tyrosine kinase inhibitor that blocks VEGF. Recent reports demonstrate clinical response in patients with metastatic bladder cancer treated with sunitinib after recurrence following standard chemotherapeutic regimens. The addition of sunitinib following BCG in order to consolidate VEGF inhibition may result in superior 3 month complete response rates. We know that patients who have a complete response to BCG at 3 months have improved disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sunitinib treatment | Experimental | Drug: SunitinibIntravesical BCG (81 mg Theracys BCG in 50 ml normal saline) once weekly for 6 weeks within 6 weeks of bladder biopsy confirming high risk non-muscle invasive urothelial carcinoma. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Patients must have histologically confirmed urothelial carcinoma confined to the urinary bladder and/or prostatic urethra by bladder biopsy within 6 weeks of study enrollment.
- Patients are eligible if the biopsy was done within 3 months of enrollment and a cystoscopy demonstrates no gross disease within 6 weeks of enrollment.
- Tumor histology with >50% transitional cell carcinoma histology
- Tumor stage less than or equal to T1 confirmed by pathology report
- Patients with a T1 tumor will require a restaging TURBT confirming no higher stage tumor prior to study enrollment
Key exclusion criteria (26 listed)
- Patients with a prior history of radiation for bladder cancer
- Patients with a prior history of radiation for prostate cancer are eligible for the study
- Greater than or equal to T2N0M0 transitional cell carcinoma of the bladder on current pathology or in the past
- Patients with a prior history of upper tract urothelial carcinoma are eligible for participation in the study as long as there is no evidence of disease for 6 months prior to study enrollment
- Patients with other malignancies are eligible for enrollment in the study but should not be on active treatment for this malignancy within 12 months of study enrollment. Patients with prior history of local treatment for prostate cancer are eligible for participation in the study
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 |
|---|---|---|
| SunitinibAlso: SutentPatients are treated with a 6-week induction course of intravesical bacillus Calmette-Guerin (BCG) followed by a 2 week rest period and 4 week course of oral Sunitinib. Patients will receive intravesical BCG (81 mg Theracys BCG in 50 ml normal saline) once weekly for 6 weeks within 6 weeks of bladder biopsy confirming high risk non-muscle invasive urothelial carcinoma. Two weeks after completion of BCG, patients will receive Sunitinib (50 mg daily) continuously for 28 days followed by a two week rest period. Patients will be reassessed with transurethral resection and urine cytology. Those with residual/recurrent disease will receive a second course identical to the initial protocol. Those with a complete response following initial or second treatment will be placed on maintenance BCG (3 week course every 6 months for 2 years). Those failing (progression, intolerance) initial/secondary treatments will be offered alternative therapy. | Drug | Sunitinib treatment |
Primary outcome
Number of Participants With Complete Response at 3 Months
Time frame: 14 weeks
Complete response is defined as no evidence of cancer on bladder biopsy or on a urine test that looks for cancer cells (cytology)
3 secondary outcomes
Percentage of Participants Who Experienced a Complete Response at 6 Months, Following Study Regimen.
Time frame: 28 weeks
Recurrence-free Survival at 2 Years in Patients With Intact Bladder.
Time frame: 2 years
Number of Participants With Toxicity Related to Treatment With BCG Followed by Sunitinib
Time frame: 26 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Alon Weizer, MD principal investigator
University of Michigan
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sunitinib in people with Urinary Tract Urothelial Carcinoma, run by University of Michigan at 2 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 22 inclusion and 26 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 23 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2019). 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?
Number of Participants With Complete Response at 3 Months (time frame: 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Sep 2019.