Clinical trial NCT01200992: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Bladder Neoplasm
Neoplasm Recurrence, Local
Transitional Cell, Carcinoma
Carcinoma in Situ
Mycobacterium
Keywords: Urinary Bladder Neoplasms
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Mycobacterial cell wall DNA complex
Intravesical drug administration
Lead sponsor: Bioniche Life Sciences Inc.
Sponsor class: INDUSTRY
First posted: 2010-09-14
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


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

Primary outcomes:
measure: Comparison of Event-free Survival of Intravesical EN3348 With Mitomycin C.
timeFrame: 1 year
Secondary outcomes:
measure: Comparison of Safety of EN3348 With Mitomycin C [Adverse Events (Other Than Serious Adverse Events) With Frequency Threshold of 5% or Greater].
timeFrame: Through study early termination, approximately 23 months from first subject enrolled.
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Clinical Research Center, LLC
state: Alaska
city: Phoenix
country: United States
facility: BCG Oncology, PC
state: Arizona
city: Tucson
country: United States
facility: Arizona Urologic Specialists
state: Arizona
city: Burbank
country: United States
facility: Urology Specialists of Southern California - Burbank
state: California
city: Encino
country: United States
facility: Urology Specialist of Southern California - Encino
state: California
city: Los Angeles
country: United States
facility: American Institute of Research
state: California
city: San Diego
country: United States
facility: San Diego Clinical Trials
state: California
city: Tarzana
country: United States
facility: West Coast Clinical Research
state: California
city: Torrance
country: United States
facility: Urology Specialists of Southern California - Torrance
state: California
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Denver
country: United States
facility: Genitourinary Surgical Consultants, PC
state: Colorado
city: Englewood
country: United States
facility: Urology Associates
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: New Britain
country: United States
facility: Grove Hill Medical Center
state: Connecticut
city: Coral Springs
country: United States
facility: Florida Urological Associates, PA
state: Florida
city: Hialeah
country: United States
facility: Urological Research Network
state: Florida
city: Ocala
country: United States
facility: Urology Health Team, PLLC
state: Florida
city: Trinity
country: United States
facility: Advanced Research Institute, Inc.
state: Florida
city: Chicago
country: United States
facility: Northwestern Medicine
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Evansville
country: United States
facility: Deaconess Clinic, Inc.
state: Indiana
city: Fort Wayne
country: United States
facility: Northeast Indiana Research, LLC
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Urology Care, P.A.
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Chesapeake Urology Research Associates
state: Maryland
city: Cumberland
country: United States
facility: Corbin Clinical Resources
state: Maryland
city: Glen Burnie
country: United States
facility: Chesapeake Urology Research Associates
state: Maryland
city: Greenbelt
country: United States
facility: Myron I. Murdock, MD, LLC
state: Maryland
city: Towson
country: United States
facility: Chesapeake Urology Research Associates
state: Maryland
city: Watertown
country: United States
facility: Bay State Urologists
state: Massachusetts
city: Troy
country: United States
facility: Michigan Institute of Urology
state: Michigan
city: Mount Laurel
country: United States
facility: Delaware Valley Urology, LLC Burlington
state: New Jersey
city: Voorhees
country: United States
facility: Delaware Valley Urology
state: New Jersey
city: Albany
country: United States
facility: The Capital Region Medical Research Foundation, Inc.
state: New York
city: Garden City
country: United States
facility: Accumed Research Associates
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group of the Hudson Valley
state: New York
city: The Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Cincinnati
country: United States
facility: TriState Urologic Services PSC, Inc.
state: Ohio
city: Columbus
country: United States
facility: Columbus Urology
state: Ohio
city: Middletown
country: United States
facility: Signal Point Clinical Research Center, LLC
state: Ohio
city: Toledo
country: United States
facility: Unison Clinical Research
state: Ohio
city: Bethany
country: United States
facility: Parkhurst Research Organization, LLC
state: Oklahoma
city: Bala-Cynwyd
country: United States
facility: Urologic Consultants of SE PA
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Urology Health Specialists, LLC
state: Pennsylvania
city: Indiana
country: United States
facility: Ilumina Clinical Associates
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Triangle Urological Group
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Physician Group
state: Pennsylvania
city: East Providence
country: United States
facility: Pharma Resource
state: Rhode Island
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Arlington
country: United States
facility: Urology Associates of North Texas
state: Texas
city: Dallas
country: United States
facility: Urology Clinics of North Texas, PA
state: Texas
city: McAllen
country: United States
facility: Urology Associates of South Texas
state: Texas
city: Richmond
country: United States
facility: Virginia Urology
state: Virginia
city: Kelowna
country: Canada
facility: Southern Interior Medical Research, Inc.
state: British Columbia
city: Victoria
country: Canada
facility: Pacific Urologic Research
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Newmarket
country: Canada
facility: Mor Urology Inc.
state: Ontario
city: North Bay
country: Canada
facility: Office of Dr. Bernard Goldfarb
state: Ontario
city: Oakville
country: Canada
facility: The Fe/Male Health Centres
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital - University Health Network
state: Ontario
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec- L'Hotel-Dieu de Quebec
state: Quebec
city: Kirchheim unter Teck
country: Germany
facility: GUT (Society of Urologic Innovative Therapies), GbR
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St Radboud, Department of Urology
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lublin
country: Poland
facility: Oddział Urologii, Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie [Department of Urology, Independent Public Teaching Hospital #4 in Lublin]
city: Warszawa
country: Poland
facility: Maria Sklodowska-Curie Institute of Oncology
city: Wroclaw
country: Poland
facility: Wojewódzki Szpital Specjalistyczny we Wrocławiu
city: Nottingham
country: United Kingdom
facility: Nottingham Urology Centre, NHS Trust
Study officials:
References: