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

Bladder Neoplasm Clinical Trial

— EMBARC-RF  

Official title:

A Phase 3, Randomized, Active-Controlled, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of EN3348 (MCC) as Compared With Mitomycin C in the Intravesical Treatment of Subjects With BCG Recurrent or Refractory Non-Muscle Invasive Bladder Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01200992
• Other study ID #: EN3348-303
• Status: Terminated
• Phase: Phase 3
• First received: September 12, 2010
• Last updated: August 23, 2017
• Start date: November 2010
• Est. completion date: December 2013

Study information

• Verified date: August 2017
• Source: Bioniche Life Sciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 3 randomized, active-controlled, open-label, multicenter study that will be conducted in approximately 120 investigational sites worldwide. Subjects with either recurrent or refractory NMIBC (Ta high grade, T1 low or high grade, CIS) will be eligible for participation in this study.

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.

Approximately 450 subjects will be randomized. The primary objective of this study is to evaluate the efficacy of intravesical EN3348 as compared with mitomycin C in the treatment of subjects with recurrent or refractory NMIBC. The secondary objective is to evaluate the safety of EN3348 as compared with mitomycin C in the treatment of subjects with BCG recurrent or refractory NMIBC. This study will consist of 4 phases: Screening, Induction, Maintenance and Follow-Up and will be conducted over 3 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 84
• Est. completion date: December 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Neoplasm
• Carcinoma
• Carcinoma in Situ
• Mycobacterium
• Mycobacterium Infections
• Neoplasm Recurrence, Local
• Neoplasms
• Recurrence
• Transitional Cell, Carcinoma
• Urinary Bladder Neoplasms

Intervention

Biological:
• EN3348
Induction: 6 weekly instillations. Maintenance: Monthly instillations to Month 12
• Mitomycin C
Induction: 6 weekly instillations. Maintenance: Monthly instillations to Month 12

Locations

Country	Name	City	State
Canada	Southern Interior Medical Research, Inc.	Kelowna	British Columbia
Canada	London Health Sciences Centre	London	Ontario
Canada	Mor Urology Inc.	Newmarket	Ontario
Canada	Office of Dr. Bernard Goldfarb	North Bay	Ontario
Canada	The Fe/Male Health Centres	Oakville	Ontario
Canada	Centre Hospitalier Universitaire de Quebec- L'Hotel-Dieu de Quebec	Quebec City	Quebec
Canada	Princess Margaret Hospital - University Health Network	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Pacific Urologic Research	Victoria	British Columbia
Germany	GUT (Society of Urologic Innovative Therapies), GbR	Kirchheim unter Teck
Netherlands	Universitair Medisch Centrum St Radboud, Department of Urology	Nijmegen
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Oddzial Urologii, Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie [Department of Urology, Independent Public Teaching Hospital #4 in Lublin]	Lublin
Poland	Maria Sklodowska-Curie Institute of Oncology	Warszawa
Poland	Wojewódzki Szpital Specjalistyczny we Wroclawiu	Wroclaw
United Kingdom	Nottingham Urology Centre, NHS Trust	Nottingham
United States	The Capital Region Medical Research Foundation, Inc.	Albany	New York
United States	Alaska Clinical Research Center, LLC	Anchorage	Alaska
United States	Urology Associates of North Texas	Arlington	Texas
United States	Urologic Consultants of SE PA	Bala-Cynwyd	Pennsylvania
United States	Chesapeake Urology Research Associates	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Parkhurst Research Organization, LLC	Bethany	Oklahoma
United States	Urology Health Specialists, LLC	Bryn Mawr	Pennsylvania
United States	Urology Specialists of Southern California - Burbank	Burbank	California
United States	Northwestern Medicine	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	TriState Urologic Services PSC, Inc.	Cincinnati	Ohio
United States	Columbus Urology	Columbus	Ohio
United States	Florida Urological Associates, PA	Coral Springs	Florida
United States	Corbin Clinical Resources	Cumberland	Maryland
United States	Urology Clinics of North Texas, PA	Dallas	Texas
United States	Genitourinary Surgical Consultants, PC	Denver	Colorado
United States	The Urology Center of Colorado	Denver	Colorado
United States	Pharma Resource	East Providence	Rhode Island
United States	Urology Specialist of Southern California - Encino	Encino	California
United States	Urology Associates	Englewood	Colorado
United States	Deaconess Clinic, Inc.	Evansville	Indiana
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Northeast Indiana Research, LLC	Fort Wayne	Indiana
United States	Accumed Research Associates	Garden City	New York
United States	Chesapeake Urology Research Associates	Glen Burnie	Maryland
United States	Myron I. Murdock, MD, LLC	Greenbelt	Maryland
United States	Urological Research Network	Hialeah	Florida
United States	Ilumina Clinical Associates	Indiana	Pennsylvania
United States	American Institute of Research	Los Angeles	California
United States	Urology Associates of South Texas	McAllen	Texas
United States	Signal Point Clinical Research Center, LLC	Middletown	Ohio
United States	Delaware Valley Urology, LLC Burlington	Mount Laurel	New Jersey
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Grove Hill Medical Center	New Britain	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Urology Health Team, PLLC	Ocala	Florida
United States	Kansas City Urology Care, P.A.	Overland Park	Kansas
United States	BCG Oncology, PC	Phoenix	Arizona
United States	Triangle Urological Group	Pittsburgh	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Premier Medical Group of the Hudson Valley	Poughkeepsie	New York
United States	Virginia Urology	Richmond	Virginia
United States	San Diego Clinical Trials	San Diego	California
United States	Mount Nittany Physician Group	State College	Pennsylvania
United States	West Coast Clinical Research	Tarzana	California
United States	Montefiore Medical Center	The Bronx	New York
United States	Unison Clinical Research	Toledo	Ohio
United States	Urology Specialists of Southern California - Torrance	Torrance	California
United States	Chesapeake Urology Research Associates	Towson	Maryland
United States	Advanced Research Institute, Inc.	Trinity	Florida
United States	Michigan Institute of Urology	Troy	Michigan
United States	Arizona Urologic Specialists	Tucson	Arizona
United States	Delaware Valley Urology	Voorhees	New Jersey
United States	Bay State Urologists	Watertown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Bioniche Life Sciences Inc.

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Netherlands,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of Event-free Survival of Intravesical EN3348 With Mitomycin C.	Primary efficacy endpoint will be event-free survival - the interval from randomization to an event. An event is defined as tumor recurrence, tumor progression to muscle invasive bladder cancer or death, whichever occurs first. Tumor recurrence or progression must be documented by bladder biopsy.	1 year
Secondary	Comparison of Safety of EN3348 With Mitomycin C [Adverse Events (Other Than Serious Adverse Events) With Frequency Threshold of 5% or Greater].	Safety endpoint displayed includes adverse events (other than serious adverse events) with a frequency threshold of 5% or greater, for each treatment arm. No statistical comparisons have been performed between the 2 treatment arms.	Through study early termination, approximately 23 months from first subject enrolled.

External Links

•   26th Annual Congress of the European Association of Urology