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.

INTRODUCTION

Org Study ID: RITE-1
Secondary ID: N/A
NCT ID: NCT03335059
Sponsor: Medical Enterprises Ltd.

This study will determine whether Synergo® RITE + MMC treatment is efficacious as second-line
therapy for CIS NMIBC BCG-unresponsive patients with or without papillary NMIBC, through
examination of the complete response rate (CRR) and disease-free duration for complete
responders. The study will also explore progression-free survival time, bladder preservation
rate, and overall survival time.

The study will address an unmet need to identify a treatment effective in both ablating the
disease and providing a prolonged disease-free period for patients. Ideally, the treatment
will delay progression to invasive disease, thus preserving the bladder.

Overall Status
Recruiting
Start Date
April 4, 2019
Phase
Phase 3
Study Type
Interventional

Primary Outcome 1 - Measure: complete response rate (CRR)

Primary Outcome 1 - Timeframe: 3 months after the initiation of study therapy

Bladder Cancer
Bladder Neoplasm
Bladder Tumors
Cancer of Bladder
Cancer of the Bladder
Malignant Tumor of Urinary Bladder
Neoplasms
Bladder
Urinary Bladder Cancer
Carcinoma in Situ of Bladder
Papillary Carcinoma of Bladder (Diagnosis)
BCG-Unresponsive Bladder Cancer

Inclusion Criteria:

1. Patients with current CIS of the bladder, with or without coexisting papillary Ta/T1
NMIBC tumor(s), who experienced an occurrence or recurrence of CIS within 12 months of
completion 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 6
weekly treatments and the second course may have included a re-induction (at least 2
of 6 treatments) or maintenance, (at least 2 of 3 treatments) administered on a
schedule similar to the SWOG 8507 study regimen.

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

1. Date of initial treatment,

2. Date of last treatment,

3. The number of courses administered and the number of treatments administered in
each course.

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

1. if the previous TUR was incomplete,

2. if there was no muscle in the specimen after the initial TUR (except in TaLG
tumors),

3. in all T1,

4. in all HG tumors ≥ 3cm.

4. CT-IVU or MRI-IVU or IVU/retrograde confirmation of absence of tumor(s) in the upper
tract, kidney and ureters performed within 6 months before the study treatment
initiation, in selected cases, as recommended in latest AUA guidelines published prior
to screening. If IVU/retrograde protocol is not available or contrast allergy/poor
renal function preclude such imaging, then non-contrast CT or MRI of the
abdomen/pelvis within the same timeframe will suffice.

5. Visual inspection to exclude urothelial carcinoma (UC) in the urethra during
cystoscopy.

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

1. tumor of trigone,

2. tumor of bladder neck, or

3. abnormal prostatic urethra

4. prior history of prostatic urethral involvement.

7. All patients must have urine cytology collected from either voided urine or bladder
wash within the screening period prior to enrollment. Patients with positive cytology
must also have selective cytology from the upper tract and prostatic urethral biopsies
collected within the same period. Patients with a localizing positive upper tract
cytology are excluded from the study until definitive treatment renders them free of
disease visually and/or radiographically and cytologically (nephroureterectomy, distal
ureterectomy or upper tract therapy).

8. Age ≥ 18 yrs.

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

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

1. Hemoglobin ≥ 10 g/dl (g/100 ml)

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

3. WBC ≥ 3.0 x 10^9/L (x 10^3/mm^3)

4. ANC ≥ 1.5 x 10^9/L (x 10^3/mm^3)

5. Serum creatinine < 2 mg/dl

6. SGOT < 1.5 x ULN

7. SGPT < 1.5 x ULN

8. Alkaline phosphatase < 1.5 x ULN

11. Negative pregnancy test for women of childbearing potential.

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

13. 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 ultrasonic
estimation of maximum bladder capacity or void spontaneously the maximum they can
retain in their bladder, and this will be used to determine urine volume. A minimum
volume of 250 ml is required.

7. Patients with severe bladder outlet obstruction not adequately controlled with
medication (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 if
sexually 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 cured
by excision, surgically treated carcinoma in situ of the cervix or ductal CIS
(DCIS)/lobular CIS (LCIS) of the breast or stable prostate cancer (under active
surveillance 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 prospective
study participant from receiving the study treatment.

15. Known untreated urethral strictural disease or bladder neck contracture or any other
condition that may prevent catheterization with a 21F catheter. Patients may undergo
dilation 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 or
Sponsor's authorized representative.

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

Name: Igal Ruvinsky, PhD

Role: Study Director

Affiliation: Medical Enterprises Ltd.

Name: Igal Ruvinsky, PhD

Phone: +972 (3) 924 48 30

Email: igal.ru@synergo-medical.com

Facility	Status	Contact
Facility: BCG Oncology Phoenix, Arizona 85032 United States	Status: Recruiting	Contact: Debbi Mobley 602-493-6626 debbi@bcgoncology.com
Facility: University of Iowa Hospitals & Clinics Iowa City, Iowa 52242 United States	Status: Recruiting	Contact: Janelle Born, RN BSN 319-356-4797 janelle-born@uiowa.edu
Facility: Chesapeake Urology Research Associates Hanover, Maryland 21076 United States	Status: Recruiting	Contact: Wendy Paxton 443-471-5763 wpaxton@cua.md
Facility: Icahn School of Medicine at Mount Sinai New York, New York 10029 United States	Status: Recruiting	Contact: Cynthia Knauer 212-241-0751 cynthia.knauer@mountsinai.org
Facility: Memorial Sloan Kettering Cancer Center New York, New York 10065 United States	Status: Recruiting	Contact: Tanya Klein, MPH 646-227-2231 kleint@mskcc.org
Facility: University of Pennsylvania Philadelphia, Pennsylvania 19104 United States	Status: Recruiting	Contact: Hanna Stambakio 215-614-5039 hanna.stambakio@uphs.upenn.edu

Brief Title: 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.

A Multicenter, Single-Arm Study Evaluating the Efficacy of Synergo® Radiofrequency-Induced Thermochemotherapy Effect (RITE) With Mitomycin C (Synergo® RITE + MMC) in CIS Non-Muscle Invasive Bladder Cancer (NMIBC) Bacillus Calmette-Guérin (BCG)-Unresponsive Patients With or Without Papillary NMIBC

INTRODUCTION

BRIEF SUMMARY

PRIMARY OUTCOMES

CONDITION

ELIGIBILITY

OFFICIAL INFORMATION

Overall Contact

LOCATION

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