Bacillus Calmette-Guerin Followed by Sunitinib for the Treatment of High Risk Non-muscle Invasive Lower Urinary Tract Urothelial Carcinoma

NCT00794950 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Sutent V5 / November 9, 2009
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 2

Brief 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 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.

Conditions

Urinary Tract Urothelial Carcinoma

Keywords

Bladder Cancer; High Risk Non-muscle Invasive Lower Urinary Tract Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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)

  14 weeks

Secondary Outcomes (3)

• Percentage of Participants Who Experienced a Complete Response at 6 Months, Following Study Regimen.

  28 weeks

• Recurrence-free Survival at 2 Years in Patients With Intact Bladder.

  2 years

• Number of Participants With Toxicity Related to Treatment With BCG Followed by Sunitinib

  26 months

Study Arms (1)

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.

Drug: Sunitinib

Interventions

Sunitinib DRUG

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.

Also known as: Sutent

Sunitinib treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (2)

Mark P. Schoenberg, MD

Baltimore, Maryland, 21287-2101, United States

Location

Alon Weizer, MD

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Alon Z. Weizer, MD, MS
• Organization: University of Michigan

aweizer@umich.edu

734-615-6662

Study Officials

• Alon Weizer, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Urology

Study Record Dates

• First Submitted: November 20, 2008
• First Posted: November 21, 2008
• Study Start: January 1, 2009
• Primary Completion: August 22, 2016
• Study Completion: August 22, 2016
• Last Updated: September 23, 2019
• Results First Posted: September 23, 2019

Record last verified: 2019-09

Locations

US (2)