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.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||April 2019||Phase 3||Interventional|
Primary Outcome 1 - Measure: complete response rate (CRR)
Primary Outcome 1 - Time Frame: 3 months after the initiation of study therapy
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 18 months of
their initial BCG treatment and within 6 months of their last BCG treatment, while on
an adequate BCG regimen. 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 (5 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
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
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
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.
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
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.
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Igal Ruvinsky, PhD
Role: Study Director
Affiliation: Medical Enterprises Ltd.
Name: Igal Ruvinsky, PhD
Phone: +972 (3) 924 48 30
Phoenix, Arizona 85032
Los Angeles, California 90048
|University of Iowa Hospitals & Clinics
Iowa City, Iowa 52242
Janelle Born, RN BSN
|Chesapeake Urology Research Associates
Hanover, Maryland 21076
|University of Pennsylvania
Philadelphia, Pennsylvania 19104