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

• Status: Completed
• Trial end date: 2016-08-22
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Michigan
• Treatments: BCG Vaccine; Sunitinib

Criteria

Inclusion Criteria:

• 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

• 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).

Exclusion Criteria:

• 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.

• 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.