Efficacy and Safety Evaluation of EN3348 (Mycobacterial Cell Wall-DNA Complex [MCC]) as Compared With Mitomycin C in the Intravesical Treatment of Subjects With BCG Recurrent/Refractory Non-muscle Invasive Bladder Cancer (EMBARC-RF)
Bladder Neoplasm, Neoplasm Recurrence, Local, Transitional Cell, Carcinoma
About this trial
This is an interventional treatment trial for Bladder Neoplasm focused on measuring Urinary Bladder Neoplasms, Neoplasms, Urologic Neoplasms, Urogenital Neoplasms, Neoplasms by Site, Urinary Bladder Diseases, Urologic Diseases, Mycobacterial cell wall DNA complex, Intravesical drug administration
Eligibility Criteria
Inclusion Criteria:
- Is 18 years of age and older at time of consent signing
Have either BCG recurrent or refractory NMIBC:
- Refractory disease is defined as evidence of persistent high grade bladder cancer (Ta HG, T1 and/or CIS) at least 6 months from the start of a full induction course of BCG with or without maintenance/re-treatment at 3 months
Recurrent disease is defined as reappearance of disease after achieving a tumor-free status by 6 months following a full induction course of BCG with or without maintenance/re-treatment at 3 months. Subjects with recurrent disease must have recurred within 18 months following the last dose of BCG
- A full induction course of BCG is defined as at least 5 out of 6 total expected instillations of BCG within a period of 2 months, regardless of dose strength
Have histologically confirmed NMIBC (according to 2004 WHO classification) within 8 weeks prior to randomization
- High grade Ta papillary lesion(s)
- High or low grade T1 papillary lesion(s)(biopsy sample must include evidence of muscularis propria)
- CIS, with or without Ta or T1 papillary tumor(s) of any grade
- Have had all visible papillary and resectable CIS lesion(s) removed by TURBT within 8 weeks prior to randomization
- Available for the duration of the study including follow-up (approximately 36 months)
- Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of 2 or less
Have no evidence of urothelial carcinoma involving the upper urinary tract or the urethra (confirmed by extravesical work up, which may include radiological imaging and/or biopsy) within 6 months of randomization:
- If previous work up occurred more than 6 months from randomization, extravesical work up must be repeated prior to randomization in order to determine eligibility
- Subjects (male and female) of child-bearing potential (including female subjects who are post-menopausal for less than 1 year) must be willing to practice effective contraception (as defined by the Investigator) during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment
- Is able to understand and give written informed consent
Exclusion Criteria:
- Current or previous history of muscle invasive bladder tumors
- Current or previous history of lymph node positive and/or metastatic bladder cancer
- Current evidence of pure squamous cell carcinoma, pure adenocarcinoma or pure undifferentiated carcinoma of the bladder
- Currently receiving systemic cancer therapy (cytotoxic/cytostatic or immunotherapy)
- Currently receiving treatment with a prohibited therapy
- Current or prior history of systemic lupus erythematosus
- Systemic immunotherapy within 6 months of randomization
- Treatment with an investigational agent within 30 days or 5 half lives from randomization, whichever is longer
- Prior treatment with an intravesical chemotherapeutic agent within 3 months of randomization except for single perioperative dose of chemotherapy immediately post-TURBT
- Prior treatment with EN3348 (MCC) or any other mycobacterial cell wall composition or formulation
- Refractory to mitomycin C (failure to achieve tumor-free status following minimum of a 6 week induction course of mitomycin C)
- Contraindication to mitomycin C
- Untreated urinary tract or bladder infection
- ANC <1000/µL and hemoglobin <10 g/dL
- Known cardiovascular disease such as myocardial infarction within the past 3 months, unstable angina pectoris, congestive heart failure (NYHA Class III or IV) or uncontrolled cardiac arrhythmia
- Female subjects who are pregnant or lactating
- Congenital or acquired immune deficiency
- Have current or history of documented or suspected malignancy of any organ system (diagnosed, treated or untreated) within the past 5 years (with the exception of localized transitional cell carcinoma of the ureter treated with ureterectomy or nephroureterectomy, adequately treated basal cell or squamous cell carcinoma of the skin or asymptomatic non-metastatic prostate cancer either previously successfully treated or currently under active surveillance or receiving hormone therapy only)
- Bladder contracture or history of an inability to retain the instillate for a minimum of 1 hour, even with premedication
- Inability to tolerate intravesical administration or intravesical surgical manipulation (cystoscopy or biopsy)
- Clinically significant active infections
- Any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial per protocol
Sites / Locations
- Alaska Clinical Research Center, LLC
- BCG Oncology, PC
- Arizona Urologic Specialists
- Urology Specialists of Southern California - Burbank
- Urology Specialist of Southern California - Encino
- American Institute of Research
- San Diego Clinical Trials
- West Coast Clinical Research
- Urology Specialists of Southern California - Torrance
- The Urology Center of Colorado
- Genitourinary Surgical Consultants, PC
- Urology Associates
- University of Connecticut Health Center
- Grove Hill Medical Center
- Florida Urological Associates, PA
- Urological Research Network
- Urology Health Team, PLLC
- Advanced Research Institute, Inc.
- Northwestern Medicine
- University of Chicago
- Deaconess Clinic, Inc.
- Northeast Indiana Research, LLC
- Kansas City Urology Care, P.A.
- University of Maryland
- Chesapeake Urology Research Associates
- Corbin Clinical Resources
- Chesapeake Urology Research Associates
- Myron I. Murdock, MD, LLC
- Chesapeake Urology Research Associates
- Bay State Urologists
- Michigan Institute of Urology
- Delaware Valley Urology, LLC Burlington
- Delaware Valley Urology
- The Capital Region Medical Research Foundation, Inc.
- Accumed Research Associates
- Columbia University Medical Center
- Premier Medical Group of the Hudson Valley
- Montefiore Medical Center
- TriState Urologic Services PSC, Inc.
- Columbus Urology
- Signal Point Clinical Research Center, LLC
- Unison Clinical Research
- Parkhurst Research Organization, LLC
- Urologic Consultants of SE PA
- Urology Health Specialists, LLC
- Ilumina Clinical Associates
- Triangle Urological Group
- University of Pittsburgh
- Mount Nittany Physician Group
- Pharma Resource
- Carolina Urologic Research Center
- Vanderbilt University Medical Center
- Urology Associates of North Texas
- Urology Clinics of North Texas, PA
- Urology Associates of South Texas
- Virginia Urology
- Southern Interior Medical Research, Inc.
- Pacific Urologic Research
- London Health Sciences Centre
- Mor Urology Inc.
- Office of Dr. Bernard Goldfarb
- The Fe/Male Health Centres
- Sunnybrook Health Sciences Centre
- Princess Margaret Hospital - University Health Network
- Centre Hospitalier Universitaire de Quebec- L'Hotel-Dieu de Quebec
- GUT (Society of Urologic Innovative Therapies), GbR
- Universitair Medisch Centrum St Radboud, Department of Urology
- Uniwersyteckie Centrum Kliniczne
- Oddział Urologii, Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie [Department of Urology, Independent Public Teaching Hospital #4 in Lublin]
- Maria Sklodowska-Curie Institute of Oncology
- Wojewódzki Szpital Specjalistyczny we Wrocławiu
- Nottingham Urology Centre, NHS Trust
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
EN3348
Mitomycin C
8 mg mixed with sterile water for injection for a total volume of 50mL
40 mg powder will be reconstituted with sterile water for injection to a total volume of 40 mL