Sunitinib Malate in Treating Patients With Recurrent Transitional Cell Bladder Cancer

PRIMARY OBJECTIVES:

I. To determine the clinical efficacy of oral sunitinib (Sutent) given continuously for a
maximum of 12 weeks, with respect to complete response rates at 12 months after completion of
treatment in patients with high-risk superficial bladder cancer who have failed previous
intravesical BCG.

SECONDARY OBJECTIVES:

I. To assess the impact of sunitinib treatment in recurrence-free survival, progression-free
survival, and overall survival in patients with high-risk superficial TCC of the bladder who
have failed previous intravesical BCG.

II. To evaluate the safety and tolerability of sunitinib (Sutent) administered in patients
with high-risk superficial TCC of the bladder who have failed previous intravesical BCG.

TERTIARY OBJECTIVES:

I. To assess pre-treatment tissue baseline angiogenic markers and to evaluate the magnitude
of the difference among these variables with post-treatment tumor tissue after treatment with
sunitinib (Sutent).

II. To evaluate the effects of Sunitinib (Sutent) on immunosuppressive regulatory T cells
(Tregs).

III. To determine the presence of circulating tumor cells in superficial BCG-refractory TCC
patients.

OUTLINE:

Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28
days for 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion

- Patients must have clinically and histologically proven, recurrent superficial
transitional cell carcinoma of the bladder after treatment with BCG therapy

- Patients could have received previous any INTRAVESICAL therapy including BCG and/or
IFN and/or chemotherapy up to 3 years prior to registration

- Patients biopsy specimen should be available for review

- ECOG PS 0-1 (Karnofsky greater than 70%)

- Absolute neutrophil count >= 1,000/mcL

- Platelets >= 100,000/mcL

- Hemoglobin >= 8.5 g/dl

- Total bilirubin =< 1.5 X institutional upper limit of normal

- AST(SGOT)/ALT(SGPT) =< 3.5 X institutional upper limit of normal

- Alkaline phosphatase =< 2.5 ULN ( =< 10 x ULN in presence of bone metastasis)

- Serum calcium of =< 12 mg/dl

- Creatinine =< 1.5 X institutional upper limit of normal

- INR =< 1.5, except for subjects receiving warfarin therapy

- Eligibility of patients receiving any medications or substances known to affect or
with the potential to affect the activity or pharmacokinetics of Sunitinib (Sutent)
will be determined following review of their case by the Principal Investigator

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation; sexually active patients must continue to use
contraception for three months after completion of study therapy; should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should inform her treating physician immediately

- All patients must be informed of the investigational nature of this study and must
provide written informed consent in accordance with institutional and federal
guidelines

Exclusion

- Prior systemic chemotherapy for bladder cancer; all other systemic chemotherapy must
have been completed at least 3 years prior to enrollment

- Prior treatment with any other anti-angiogenic therapy (including immunomodulatory
agents such as thalidomide and lenalidomide, and anti-VEGF therapy with agents such as
bevacizumab (Bevacizumab Avastin, Sunitinib (Sutent) and Sorafenib (Nexavar)

- Prior major surgery (not TURBT/Cystoscopy), radiation therapy, or systemic therapy
within 4 weeks of starting the study treatment

- NCI CTCAE grade 3 hemorrhage within 4 weeks of starting study treatment

- 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, cerebrovascular accident or transient
ischemic attack, or pulmonary embolism

- Ongoing cardiac dysrhythmias of NCI CTCAE grade >= 2, or prolongation of the QTc
interval to > 450 msec for males or > 470 msec for females (Atrial Fibrillation is
allowed provided patients are rated controlled)

- Hypertension that cannot be controlled by medications

- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
- related illness or infectious hepatitis type A, B or C

- Disease-free of prior malignancies for >= 2 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix

- 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

- Pregnancy or breastfeeding (Female patients must be surgically sterile or
postmenopausal, or must agree to use effective contraception during the period of
therapy; all female patients with reproductive potential must have a negative
pregnancy test [serum or urine] prior to enrollment)

- Male patients 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)