Robot-Assisted Laparoscopic High-Intensity Focused Ultrasound and Radical Cystectomy for Thermal Ablation of Muscle Invasive Cells in Patients With Bladder Tumors

PRIMARY OBJECTIVES:

I. To obtain preliminary estimates of the efficacy of laparoscopic high-intensity focused
ultrasound (HIFU) for the treatment of localized primary bladder cancer.

II. To estimate the change in the number of expelled circulating tumor cells (CTCs), when
comparing HIFU to robot-assisted radical cystectomy (RARC) alone.

SECONDARY OBJECTIVES:

I. To evaluate the safety and toxicity of using laparoscopic HIFU.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo pre-HIFU contrast-enhanced ultrasound (CEUS), standard of care biopsy
of the bladder tumor, laparoscopic HIFU, and post-HIFU CEUS. Patients then undergo standard
of care RARC.

ARM B: Patients undergo standard of care RARC.

After completion of study, patients are followed up at 2 weeks and 3 months.

Inclusion Criteria:

- Must meet all inclusion and exclusion criteria

- Presence of a muscle invasive bladder tumor(s) (T2), specific for transitional cell
carcinoma on pre-operative histology (i.e. biopsy or transurethral resection of
bladder tumor [TURBT]).

- Presence of a single bladder tumor lesion

- Patients are scheduled to undergo RARC at our institution

- Subjects must have given written informed consent to agree to participate

- Previous chemotherapy, and/or biological therapy for cancer are permitted provided
that the acoustic properties of the tumor were not affected, but the subject should
have recovered from the effects of these or of any prior surgery; chemotherapy can be
within 70 days of operation

- Subjects must be free of any clinically significant disease other than cancer that
would interfere with the study evaluations

- Pre-operative computed tomography (CT)/magnetic resonance imaging (MRI) abdomen and
pelvis within 90 days

- Absolute neutrophil count (ANC) >= 1500 mm^-3

- Platelet count >= 100,000 mm^-3

- Hemoglobin >= 10 g/dl

- Prothrombin time (PT) =< 1.5 times upper limit of laboratory normal (ULN)

- Activated partial thromboplastin time =< 1.5 times ULN

- Total bilirubin < 1.5 times ULN

- Aspartate aminotransferase (AST) =< 3 times ULN

- Alkaline phosphatase < 2 times ULN, unless arising from bone

Exclusion Criteria:

- Subjects deemed unsuitable candidates and not medically optimized for RARC

- Subjects with tumors lying < 1 cm from sensitive structures such as the ureter,
prostate or adjacent bowel

- Patients with presence of multiple bladder lesions

- Subjects on concurrent anticoagulant, or immunosuppressive medication

- Patients with pre-operative histologic confirmation of a bladder lesion other than
transitional cell carcinoma

- Subjects on anti-cancer medication whether biologic or pharmaceutical

- Women who are pregnant or nursing (pregnancy test to be performed within 24 hours
prior to HIFU treatment)

- Subjects assessed by consultant anesthetist as unsuitable for general anesthetic

- Absolute contraindications: venous injury at the level of the femoral veins or
proximally; known or suspected thrombosis of the femoral or iliac veins on the
proposed side of venous cannulation, ambulatory patient

- Relative contraindications: presence of bleeding disorders; distortion of anatomy due
to local injury or deformity; previous long-term venous catheterization; history of
vasculitis; previous injection of sclerosis agents; previous radiation therapy