Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.

Inclusion Criteria:

1. Patients with current CIS of the bladder, with or without coexisting papillary Ta/T1NMIBC tumor(s), who experienced an occurrence or recurrence of CIS within 12 months ofcompletion of adequate BCG7 therapy. An adequate BCG regimen shall consist of at least 2 courses of BCG where the first course (induction) must have included at least 5 of 6weekly treatments and the second course may have included a re-induction (at least 2of 6 treatments) or maintenance, (at least 2 of 3 treatments) administered on aschedule similar to the SWOG 8507 study regimen.

2. All clinical, intra-operative and pathological items for the AUA risk stratificationmust be documented. This includes bladder mapping, according to the instructionsspecified in the protocol. With regard to BCG and/or other NMIBC treatmentsdocumentation must include:

3. Date of initial treatment,

4. Date of last treatment,

5. The number of courses administered and the number of treatments administered ineach course.

6. Patients with concomitant papillary tumor(s) must have undergone a repeat TUR 2-4weeks prior to the first study treatment:

7. if the previous TUR was incomplete,

8. if there was no muscle in the specimen after the initial TUR (except in TaLGtumors),

9. in all T1,

10. in all HG tumors ≥ 3cm.

11. CT-IVU or MRI-IVU or IVU/retrograde confirmation of absence of tumor(s) in the uppertract, kidney and ureters performed within 6 months before the study treatmentinitiation, in selected cases, as recommended in latest AUA guidelines published priorto screening. If IVU/retrograde protocol is not available or contrast allergy/poorrenal function preclude such imaging, then non-contrast CT or MRI of theabdomen/pelvis within the same timeframe will suffice.

12. Visual inspection to exclude urothelial carcinoma (UC) in the urethra duringcystoscopy.

13. Biopsy of the prostatic urethra, prior to enrollment, to exclude UC of the prostaticurethra, in male patients with:

14. tumor of trigone,

15. tumor of bladder neck, or

16. abnormal prostatic urethra

17. prior history of prostatic urethral involvement.

18. All patients must have urine cytology collected from either voided urine or bladderwash within the screening period prior to enrollment. Patients with positive cytologymust also have selective cytology from the upper tract and prostatic urethral biopsiescollected within the same period. Patients with a localizing positive upper tractcytology are excluded from the study until definitive treatment renders them free ofdisease visually and/or radiographically and cytologically (nephroureterectomy, distalureterectomy or upper tract therapy).

19. Age ≥ 18 yrs.

20. No evidence of urothelial cancer in either kidneys or ureters.

21. Pre-treatment hematology and biochemistry values within the limits:

22. Hemoglobin ≥ 10 g/dl (g/100 ml)

23. Platelets ≥ 150 x 10^9/L (x 10^3/mm^3)

24. WBC ≥ 3.0 x 10^9/L (x 10^3/mm^3)

25. ANC ≥ 1.5 x 10^9/L (x 10^3/mm^3)

26. Serum creatinine < 2 mg/dl

27. SGOT < 1.5 x ULN

28. SGPT < 1.5 x ULN

29. Alkaline phosphatase < 1.5 x ULN

30. Negative pregnancy test for women of childbearing potential.

31. A life expectancy at least of the duration of the study.

32. Signed informed consent.

Exclusion Criteria:

1. Non-UC tumor of the urinary tract.

2. Upper tract and/or intramural tumors (e.g., in ostium).

3. Positive selective cytology from the upper tract.

4. History of stage > T1 UC.

5. Papillary tumors > T1 in repeat TUR.

6. Known or suspected reduced bladder capacity. Patients will have an ultrasonicestimation of maximum bladder capacity or void spontaneously the maximum they canretain in their bladder, and this will be used to determine urine volume. A minimumvolume of 250 ml is required.

7. Patients with severe bladder outlet obstruction not adequately controlled withmedication (AUA symptom score ≥ 20).

8. Bleeding disorder.

9. Gross hematuria within the past 2 weeks before treatment start.

10. Lactating women.

11. Women of childbearing potential unwilling or unable to use adequate contraception ifsexually active.

12. More than low-dose methotrexate (>17.5 mg once a week).

13. Other malignancy within the past 5 years, except: non melanomatous skin cancer curedby excision, surgically treated carcinoma in situ of the cervix or ductal CIS (DCIS)/lobular CIS (LCIS) of the breast or stable prostate cancer (under activesurveillance or hormone control) with a life expectancy of more than 5 years.

14. Any known allergy (e.g., to MMC) or adverse event that would prevent a prospectivestudy participant from receiving the study treatment.

15. Known untreated urethral strictural disease or bladder neck contracture or any othercondition that may prevent catheterization with a 21F catheter. Patients may undergodilation or urethral incision before entering the study.

16. Bladder diverticulum with diameter > 1cm, as determined by CT or cystography

17. UTI at any time within 3 weeks before study treatment initiation.

18. Significant urinary incontinence (spontaneous, requiring use of > 1 pad/day (PPD)).

19. History of pelvic irradiation.

20. Patients with electronic devices implanted in abdominal cavity.

21. Participation in another study, unless discussed with and approved by the Sponsor orSponsor's authorized representative.